Affiliation:
1. Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Shanxi University Taiyuan China
2. School of Life Science Shanxi University Taiyuan China
Abstract
AbstractBACKGROUNDQuinoa contains far more nutrients than any traditional grain crop. It is known that terpenoids in quinoa have anti‐inflammatory and antitumor effects, but their role in reversing drug resistance remains unclear.RESULTSOur previous studies showed that quinoa‐derived terpenoid compounds (QBT) can inhibit the occurrence and development of colon cancer. This study further indicates that QBT markedly reverse drug resistance of colon cancer. The results showed that QBT combined with 5‐fluorouracil (5‐Fu) treatment significantly enhanced the chemotherapy sensitivity of HCT‐8/Fu, compared with 5‐Fu treatment alone. Moreover, we found that QBT significantly reduced the expression of drug‐resistant proteins (P‐gp, MRP1, BCRP), and increased the accumulation of chemotherapy drugs. Taking P‐gp as the target for biogenesis prediction analysis, results showed that upregulation of miR‐495‐3p enhanced the chemosensitivity of drug‐resistant HCT‐8/Fu cells. Besides, the results showed that miR‐495‐3p was abnormally methylated in HCT‐8/Fu compared with HCT‐8 colon cancer cells. The expression of methyltransferases DNMT1, DNMT3a and DNMT3b was abnormal. After QBT treatment, the expression level of methyltransferases returned to normal. In addition, the QBT + 5Fu group showed inhibition of tumors in nude mice.CONCLUSIONQBT treatment downregulated the expression of drug‐resistant protein P‐gp by inhibiting the methylation of miR‐495‐3p, and enhanced the accumulation of 5‐Fu in vivo, which in turn reversed its chemoresistance. This suggests that QBT has potential ability as a new drug‐resistance reversal agent in colorectal cancer. © 2024 Society of Chemical Industry.