Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis.

Abstract

This research aims to explore the role of Tanshinone IIA (Tan IIA) and microRNA (miR)-30b-5p in chemoresistance of colorectal cancer (CRC). The expression levels of miR-30b-5p and apoptosis and caspase activation inhibitor (AVEN) was detected by reverse transcription-quantitative polymerase chain reaction assay. The cell proliferation and apoptosis were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The target relationship between miR-30b-5p and AVEN was confirmed by Dual-luciferase reporter assay. Transwell assay was performed to assess CRC cells' metastasis. Western blot was carried out to measure the apoptosis-related protein. The results showed that miR-30b-5p was lowly expressed in oxaliplatin-resistance CRC cells SW480 (SW480/R) compared to SW480 cells. Overexpression of miR-30b-5p significantly suppressed the malignant biological behaviors of SW480/R cells and significantly promoted the sensitivity of SW480/R cells to oxaliplatin by down-regulated AVEN expression. Besides, Tan IIA treatment upregulated miR-30b-5p expression in SW480/R cells. Moreover, miR-30b-5p upregulation strengthened the promoting effect of Tan IIA on the sensitivity of SW480/R cells to oxaliplatin. In conclusion, Tan IIA and miR-30b-5p could reverse oxaliplatin resistance of CRC cells and may thus be potential treatment strategies for treating patients with CRC.