Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis

• Published in: International journal of molecular sciences 2020-10, Vol.21 (20), p.7469
• Main Authors: Lim, Jin Hong, Choi, Kyung Hwa, Kim, Soo Young, Park, Cheong Soo, Kim, Seok-Mo, Park, Ki Cheong
• Format: Article
• Language: English
• Subjects: Aged; Angiogenesis; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Cancer therapies; Cell cycle; Cell Line, Tumor; Colon; Colon cancer; Colonic Neoplasms - etiology; Colonic Neoplasms - metabolism; Colorectal cancer; Deoxyribonucleic acid; DNA; DNA microarrays; DNA repair; Dose-Response Relationship, Drug; Drug resistance; Drug Resistance, Neoplasm - drug effects; Epigenetics; Epithelial-Mesenchymal Transition - drug effects; Female; Fibroblasts; Gene expression; Gene Expression Profiling; Genetic analysis; Genomes; Growth factors; Humans; Immunohistochemistry; In vivo methods and tests; Insulin; lenvatinib; Male; Mesenchyme; Metastases; Metastasis; Mice; Middle Aged; Mutation; Neovascularization, Pathologic - genetics; Oxaliplatin; Oxaliplatin - pharmacology; patient-derived colon cancer; Patients; Permeability; Phenylurea Compounds - pharmacology; Proteins; Quinolines - pharmacology; Tumors; Xenografts; Xenotransplantation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21207469

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.