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...
Ausführliche Beschreibung
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] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Übergeordnetes Werk: |
In: Cancers - MDPI AG, 2010, 12(2020), 9, p 2500 |
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Übergeordnetes Werk: |
volume:12 ; year:2020 ; number:9, p 2500 |
Links: |
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DOI / URN: |
10.3390/cancers12092500 |
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Katalog-ID: |
DOAJ044367155 |
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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 |
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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 |
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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 |
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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 |
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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. |
collection_details |
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container_issue |
9, p 2500 |
title_short |
PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells |
url |
https://doi.org/10.3390/cancers12092500 https://doaj.org/article/9efcb04f70f348ca90545afc62f2cc4c https://www.mdpi.com/2072-6694/12/9/2500 https://doaj.org/toc/2072-6694 |
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Kui-Jin Kim Ji Hea Sung Milang Nam Koung Jin Suh Ji-Won Kim Se Hyun Kim Jin Won Kim Yu Jung Kim Keun-Wook Lee Jong Seok Lee Jee Hyun Kim |
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Kui-Jin Kim Ji Hea Sung Milang Nam Koung Jin Suh Ji-Won Kim Se Hyun Kim Jin Won Kim Yu Jung Kim Keun-Wook Lee Jong Seok Lee Jee Hyun Kim |
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doi_str |
10.3390/cancers12092500 |
callnumber-a |
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up_date |
2024-07-03T22:38:57.920Z |
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