PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells

Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were sele...
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Autor*in:	Hyun Jung Lee [verfasserIn] Kui-Jin Kim [verfasserIn] Ji Hea Sung [verfasserIn] Milang Nam [verfasserIn] Koung Jin Suh [verfasserIn] Ji-Won Kim [verfasserIn] Se Hyun Kim [verfasserIn] Jin Won Kim [verfasserIn] Yu Jung Kim [verfasserIn] Keun-Wook Lee [verfasserIn] Jong Seok Lee [verfasserIn] Jee Hyun Kim [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	colorectal cancer abemaciclib BYL719 (Alpelisib) cell cycle inhibition anti-proliferative effect migration inhibition

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 12(2020), 9, p 2500
Übergeordnetes Werk:	volume:12 ; year:2020 ; number:9, p 2500

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers12092500

Katalog-ID:	DOAJ044367155

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allfields	10.3390/cancers12092500 doi (DE-627)DOAJ044367155 (DE-599)DOAJ9efcb04f70f348ca90545afc62f2cc4c DE-627 ger DE-627 rakwb eng RC254-282 Hyun Jung Lee verfasserin aut PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer. colorectal cancer abemaciclib BYL719 (Alpelisib) cell cycle inhibition anti-proliferative effect migration inhibition Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kui-Jin Kim verfasserin aut Ji Hea Sung verfasserin aut Milang Nam verfasserin aut Koung Jin Suh verfasserin aut Ji-Won Kim verfasserin aut Se Hyun Kim verfasserin aut Jin Won Kim verfasserin aut Yu Jung Kim verfasserin aut Keun-Wook Lee verfasserin aut Jong Seok Lee verfasserin aut Jee Hyun Kim verfasserin aut In Cancers MDPI AG, 2010 12(2020), 9, p 2500 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:9, p 2500 https://doi.org/10.3390/cancers12092500 kostenfrei https://doaj.org/article/9efcb04f70f348ca90545afc62f2cc4c kostenfrei https://www.mdpi.com/2072-6694/12/9/2500 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 9, p 2500
spelling	10.3390/cancers12092500 doi (DE-627)DOAJ044367155 (DE-599)DOAJ9efcb04f70f348ca90545afc62f2cc4c DE-627 ger DE-627 rakwb eng RC254-282 Hyun Jung Lee verfasserin aut PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer. colorectal cancer abemaciclib BYL719 (Alpelisib) cell cycle inhibition anti-proliferative effect migration inhibition Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kui-Jin Kim verfasserin aut Ji Hea Sung verfasserin aut Milang Nam verfasserin aut Koung Jin Suh verfasserin aut Ji-Won Kim verfasserin aut Se Hyun Kim verfasserin aut Jin Won Kim verfasserin aut Yu Jung Kim verfasserin aut Keun-Wook Lee verfasserin aut Jong Seok Lee verfasserin aut Jee Hyun Kim verfasserin aut In Cancers MDPI AG, 2010 12(2020), 9, p 2500 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:9, p 2500 https://doi.org/10.3390/cancers12092500 kostenfrei https://doaj.org/article/9efcb04f70f348ca90545afc62f2cc4c kostenfrei https://www.mdpi.com/2072-6694/12/9/2500 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 9, p 2500
allfields_unstemmed	10.3390/cancers12092500 doi (DE-627)DOAJ044367155 (DE-599)DOAJ9efcb04f70f348ca90545afc62f2cc4c DE-627 ger DE-627 rakwb eng RC254-282 Hyun Jung Lee verfasserin aut PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer. colorectal cancer abemaciclib BYL719 (Alpelisib) cell cycle inhibition anti-proliferative effect migration inhibition Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kui-Jin Kim verfasserin aut Ji Hea Sung verfasserin aut Milang Nam verfasserin aut Koung Jin Suh verfasserin aut Ji-Won Kim verfasserin aut Se Hyun Kim verfasserin aut Jin Won Kim verfasserin aut Yu Jung Kim verfasserin aut Keun-Wook Lee verfasserin aut Jong Seok Lee verfasserin aut Jee Hyun Kim verfasserin aut In Cancers MDPI AG, 2010 12(2020), 9, p 2500 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:9, p 2500 https://doi.org/10.3390/cancers12092500 kostenfrei https://doaj.org/article/9efcb04f70f348ca90545afc62f2cc4c kostenfrei https://www.mdpi.com/2072-6694/12/9/2500 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 9, p 2500
allfieldsGer	10.3390/cancers12092500 doi (DE-627)DOAJ044367155 (DE-599)DOAJ9efcb04f70f348ca90545afc62f2cc4c DE-627 ger DE-627 rakwb eng RC254-282 Hyun Jung Lee verfasserin aut PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer. colorectal cancer abemaciclib BYL719 (Alpelisib) cell cycle inhibition anti-proliferative effect migration inhibition Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kui-Jin Kim verfasserin aut Ji Hea Sung verfasserin aut Milang Nam verfasserin aut Koung Jin Suh verfasserin aut Ji-Won Kim verfasserin aut Se Hyun Kim verfasserin aut Jin Won Kim verfasserin aut Yu Jung Kim verfasserin aut Keun-Wook Lee verfasserin aut Jong Seok Lee verfasserin aut Jee Hyun Kim verfasserin aut In Cancers MDPI AG, 2010 12(2020), 9, p 2500 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:9, p 2500 https://doi.org/10.3390/cancers12092500 kostenfrei https://doaj.org/article/9efcb04f70f348ca90545afc62f2cc4c kostenfrei https://www.mdpi.com/2072-6694/12/9/2500 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 9, p 2500
allfieldsSound	10.3390/cancers12092500 doi (DE-627)DOAJ044367155 (DE-599)DOAJ9efcb04f70f348ca90545afc62f2cc4c DE-627 ger DE-627 rakwb eng RC254-282 Hyun Jung Lee verfasserin aut PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer. colorectal cancer abemaciclib BYL719 (Alpelisib) cell cycle inhibition anti-proliferative effect migration inhibition Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kui-Jin Kim verfasserin aut Ji Hea Sung verfasserin aut Milang Nam verfasserin aut Koung Jin Suh verfasserin aut Ji-Won Kim verfasserin aut Se Hyun Kim verfasserin aut Jin Won Kim verfasserin aut Yu Jung Kim verfasserin aut Keun-Wook Lee verfasserin aut Jong Seok Lee verfasserin aut Jee Hyun Kim verfasserin aut In Cancers MDPI AG, 2010 12(2020), 9, p 2500 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:9, p 2500 https://doi.org/10.3390/cancers12092500 kostenfrei https://doaj.org/article/9efcb04f70f348ca90545afc62f2cc4c kostenfrei https://www.mdpi.com/2072-6694/12/9/2500 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 9, p 2500
language	English
source	In Cancers 12(2020), 9, p 2500 volume:12 year:2020 number:9, p 2500
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author	Hyun Jung Lee
spellingShingle	Hyun Jung Lee misc RC254-282 misc colorectal cancer misc abemaciclib misc BYL719 (Alpelisib) misc cell cycle inhibition misc anti-proliferative effect misc migration inhibition misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells
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topic_title	RC254-282 PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells colorectal cancer abemaciclib BYL719 (Alpelisib) cell cycle inhibition anti-proliferative effect migration inhibition
topic	misc RC254-282 misc colorectal cancer misc abemaciclib misc BYL719 (Alpelisib) misc cell cycle inhibition misc anti-proliferative effect misc migration inhibition misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc colorectal cancer misc abemaciclib misc BYL719 (Alpelisib) misc cell cycle inhibition misc anti-proliferative effect misc migration inhibition misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells
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title_sort	pi3k p110α blockade enhances anti-tumor efficacy of abemaciclib in human colorectal cancer cells
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title_auth	PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells
abstract	Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer.
abstractGer	Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer.
abstract_unstemmed	Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer.
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We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of <i<PIK3CA</i< mutation status but showed greater efficacy in the <i<PIK3CA</i< mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. 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PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells

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