Matrine inhibits miR-181a-mediated chemoresistance in rectal cancer

Abstract

Chemotherapy is widely used for treating rectal cancer, but the existence of drug resistance during chemotherapy hinders the therapeutic effect of chemotherapy. Studies have found that matrine inhibits miR-181a and PI3K-Akt and the expression of miR-181a affects PI3K-Akt activity. Therefore, this paper explores whether matrine can affect PI3K-Akt activity by regulating miR-181a via constructing a rat model of rectal cancer, and finally reduce the chemotherapy resistance of rectal cancer. The rat model of rectal cancer was constructed, treated with the chemotherapy drug pentafluorouracil (5-FU), and assigned into model group, chemotherapy-resistant group, low-dose and high-dose matrine group followed by analysis of the pathology by HE staining. Rectal cancer tissues were used to construct miR-181a silencing group and miR-181a overexpression group followed by measuring cell inhibition by MTT assay, cell proliferation and apoptosis by flow cytometry, and the levels of miR-181a, PI3K and Akt. (1) miR-181a expression was related to matrine’s inhibition of chemotherapy resistance in rectal cancer; (2) miR-181a expression induced PI3K-Akt signaling during matrine’s inhibition of chemotherapy resistance; (3) matrine can further inhibit PI3K-Akt activation by inhibiting miR-181a to enhance the sensitivity of chemotherapy resistance. Matrine can inhibit the expression of miR-181a to reduce PI3K-AKT signaling activity and decrease chemotherapy resistance of rectal cancer. It provides a new idea for clinical chemotherapy drugs to treat rectal cancer and increases the therapeutic effects.