Abstract. The present study aimed to investigate the association between breast cancer susceptibility gene 1 (BRCA1) expression and drug resistance in colon cancer, with the specific aim of elucidating the underlying molecular mechanisms of vincristine (VCR) resistance in tumor cells. The HCT-8 human colon cancer cell line was used to establish the VCR-resistant HCT-8/V line by gradually increasing the concentration of VCR during cell culture. The relative mRNA and protein expression levels of BRCA1 in these colon cancer cell lines was assessed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. Resistance to VCR was established in the HCT-8/V colon cancer cells, and RT-qPCR and western blot analysis revealed the expression of BRCA1 to be significantly higher in the VCR-resistant cells compared with their drug-sensitive counterparts (P<0.05). The decreased BRCA1 expression in these VCR-resistant cells may be associated with the drug resistance frequently observed in colon cancer. IntroductionColon cancer is one of the most common malignant tumors of the digestive system. With economic development and changes in lifestyle, the incidence of colon cancer is increasing, endangering human life and health (1). Chemotherapy is an important treatment strategy for colon cancer (2); however, it is a long process involving drug combinations and the administration of large doses of drugs. Tumor drug resistance has become increasingly frequent and is a problem for the treatment of colon cancer and other malignant tumors (3). Notably, 90% of cancer mortalities are associated with tumor drug resistance (4), therefore the underlying molecular mechanisms regulating the development of drug resistance are a key focus of malignant tumor research. Mechanisms of drug resistance in tumors include the modification of drug targets, repair of damaged cells, and the activation or inhibition of cell death signaling pathways. These processes can result from gene mutations, deletions or amplifications, in addition to epigenetic changes that occur via abnormal DNA methylation or the post-transcriptional regulation of microRNAs (miRNAs) (5-7).Vincristine (VCR), the most frequently used chemotherapy drug in the clinical treatment of colon cancer, is a cell cycle-specific drug that binds to tubulin, thereby inhibiting the assembly of microtubule structures and arresting mitosis in metaphase (8). The tumor suppressor breast cancer susceptibility gene 1 (BRCA1) confers increased susceptibility to breast and ovarian cancers, and mutations in the BRCA1 gene are present in ≤50% of inherited breast cancers (9,10). In women <50 years old, the risk of colorectal cancer is increased in carriers of BRCA1 mutations (11).In the current study, the expression of BRCA1 was verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and western blotting, to investigate the role of BRCA1 in modulating VCR resistance. The findings reported here demonstrate potential...
Abstract. In a previous study, the suppressor of IKBKE 1 expression level was confirmed to be higher in vincristine (VCR)-resistant HCT-8 (HCT-8/V) colon cancer cells than in non-VCR-resistant HCT-8 cells. In the current study, IKBKE 1 expression in VCR-resistant colon cancer cells was investigated further. HCT-8 and HCT-8/V human colon cancer cells were used, and polymerase chain reaction (PCR) primers were designed to amplify the IKBKE 1 gene. Fluorescence reverse transcription-quantitative PCR (RT-qPCR) was performed to detect differences in IKBKE 1 expression between sensitive and drug-resistant colon cancer cell lines. Western blotting was performed to further observe IKBKE 1 expression. Based on the RT-qPCR and western blot results, IKBKE 1 expression was observed to be markedly higher in the HCT-8/V cells, and this difference was significant (P<0.05). Thus, IKBKE 1 expression was identified to be associated with the resistance of colon cancer cells to VCR.
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