关键词: 前列腺癌, miR-503, TLR4, 多西紫杉醇, 耐药

Abstract: Background and purpose: In the standard chemotherapy for prostate cancer, docetaxel (DTX) resistance is one of the important causes of death in patients. However, the potential mechanism of DTX chemoresistance is still unclear. Therefore, this study aimed to explore the potential mechanism of DTX resistance in prostate cancer. Methods: A total of 40 patients with prostate cancer who received chemotherapy in the Wuhan Third hospital, including 20 patients with resistance and 20 patients with sensitivity to DTX, were enrolled, and the tumor tissues were collected during surgery. The resistant cells PC-3/DTX were PC-3 cells induced by DTX. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was performed to detect the mRNA expressions of miR-503 and TLR4. Western blot was conducted to detect TLR4 protein expression. The interaction between miR-503 and TLR4 was determined by luciferase reporter assay. Cell viability and apoptosis were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results: The expression of miR-503 was decreased (P=0.013), while TLR4 was increased in the resistant tissues and cells (P=0.005 6). Overexpression of miR-503 suppressed cell viability, induced cell apoptosis, and inhibited expression of drug resistance-related protein MDR-1. Furthermore, overexpression of TLR4 reversed the effects of miR-503 overexpression. Conclusion: miR-503 targets TLR4 to regulate its expression, and affects resistance to DTX in prostate cancer.

Key words: Prostate cancer, miR-503, TLR4, Docetaxel, Resistance