1. Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis
- Author
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Sooyoung Kim, Jin Hong Lim, Kyung Hwa Choi, Ki Cheong Park, Cheong Soo Park, and Seok Mo Kim
- Subjects
Male ,Colorectal cancer ,Angiogenesis ,lenvatinib ,lcsh:Chemistry ,Mice ,angiogenesis ,chemistry.chemical_compound ,lcsh:QH301-705.5 ,Spectroscopy ,Neovascularization, Pathologic ,General Medicine ,Middle Aged ,Immunohistochemistry ,Computer Science Applications ,Colonic Neoplasms ,Quinolines ,Female ,Lenvatinib ,medicine.drug ,Epithelial-Mesenchymal Transition ,Antineoplastic Agents ,Article ,Catalysis ,Inorganic Chemistry ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Physical and Theoretical Chemistry ,Molecular Biology ,Aged ,drug resistance ,Dose-Response Relationship, Drug ,patient-derived colon cancer ,business.industry ,Gene Expression Profiling ,Phenylurea Compounds ,oxaliplatin ,Organic Chemistry ,Cancer ,medicine.disease ,Oxaliplatin ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,Drug Resistance, Neoplasm ,Cancer cell ,Cancer research ,business - Abstract
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.
- Published
- 2020
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