Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis
Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. T...
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| Language: | English |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/20/7469 |
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| author | Jin Hong Lim Kyung Hwa Choi Soo Young Kim Cheong Soo Park Seok-Mo Kim Ki Cheong Park |
| author_facet | Jin Hong Lim Kyung Hwa Choi Soo Young Kim Cheong Soo Park Seok-Mo Kim Ki Cheong Park |
| author_sort | Jin Hong Lim |
| collection | DOAJ |
| description | Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer. |
| first_indexed | 2024-03-10T15:43:40Z |
| format | Article |
| id | doaj.art-a40fa1a7229f49bb814cd26c067bb435 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:43:40Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a40fa1a7229f49bb814cd26c067bb4352023-11-20T16:36:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120746910.3390/ijms21207469Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated AngiogenesisJin Hong Lim0Kyung Hwa Choi1Soo Young Kim2Cheong Soo Park3Seok-Mo Kim4Ki Cheong Park5Gangnam Severance Hospital, Department of Surgery Yonsei, University College of Medicine 211 Eonjuro, Gangnam-gu, Seoul 135-720, KoreaDepartment of Urology, CHA Bundang Medical Center, CHA University, Seongnam 463-712, KoreaGangnam Severance Hospital, Department of Surgery Yonsei, University College of Medicine 211 Eonjuro, Gangnam-gu, Seoul 135-720, KoreaGangnam Severance Hospital, Department of Surgery Yonsei, University College of Medicine 211 Eonjuro, Gangnam-gu, Seoul 135-720, KoreaGangnam Severance Hospital, Department of Surgery Yonsei, University College of Medicine 211 Eonjuro, Gangnam-gu, Seoul 135-720, KoreaDepartment of Surgery, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 120-752, KoreaCancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer.https://www.mdpi.com/1422-0067/21/20/7469patient-derived colon cancerdrug resistanceoxaliplatinlenvatinibangiogenesis |
| spellingShingle | Jin Hong Lim Kyung Hwa Choi Soo Young Kim Cheong Soo Park Seok-Mo Kim Ki Cheong Park Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis International Journal of Molecular Sciences patient-derived colon cancer drug resistance oxaliplatin lenvatinib angiogenesis |
| title | Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis |
| title_full | Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis |
| title_fullStr | Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis |
| title_full_unstemmed | Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis |
| title_short | Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis |
| title_sort | patient derived drug resistant colon cancer cells evade chemotherapeutic drug effects via the induction of epithelial mesenchymal transition mediated angiogenesis |
| topic | patient-derived colon cancer drug resistance oxaliplatin lenvatinib angiogenesis |
| url | https://www.mdpi.com/1422-0067/21/20/7469 |
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