| Popis: |
Drug resistance limits the effectiveness of chemotherapy in colorectal cancer (CRC). Consequently, finding appropriate strategies for re-sensitizing chemo-resistant cells is crucial. Our present study aimed at taking advantage of chemotherapy and gene therapy by restoring microRNA-145 expression in oxaliplatin resistant CRC cells. Bioinformatic analysis of clinical colorectal cancer tissue revealed that miR-145 levels were significantly lower than in adjusted tumors. Afterward, pCMV-miR-145 vectors were transfected into the oxaliplatin-resistant SW-480 CRC cells. Using miR-145 and Oxaliplatin together to treat Oxaliplatin-resistant cells, the results showed significant differences in viability, proliferation, apoptosis and migration compared to the individual treatments. Furthermore, miRNA prediction results as well as mRNA and protein expression indicated that miR-145 targeted ABCC1. Also, mRNA expression analysis was performed to evaluate a panel of genes involved in cell viability, apoptosis, motility, and drug resistance. These genes included K-ras, Bcl2, CASP3, -8, -9, MMP13, MDR-1, and ABCC1. These expression changes tended towards apoptosis induction and decreased proliferation and migration. Based on our findings, miR-145 restoration via decreasing the drug resistance biomarkers ABBCC1 and MDR1, along with other oncogenes such as K-Ras and Bcl2, and increasing apoptosis conductores could sensitize oxaliplatin-resistant cells to chemotherapy. |
