Schizandrin A enhances chemosensitivity of colon carcinoma cells to 5-fluorouracil through up-regulation of miR-195

Nowadays 5-fluorouracil (5-FU)-based adjuvant chemotherapy is widely used for treating colon carcinoma. However, 5-FU resistance in the treatment of colon carcinoma has become more common and thereby new therapeutic strategies and new adjuvant drugs still need to be explored. Two 5-FU-resistant colon cancer cell lines, HCT116 and SW480, were used to investigate the effects of Schizandrin A (SchA), 5-FU, or their combination on cell viability and apoptosis. Besides, the role of miR-195 was studied to further clarify the specific function of SchA. CCK-8 assay and flow cytometry analysis were conducted to determine cell viability and apoptosis, respectively. miR-195 expression was determined by quantitative real-time PCR. Cell apoptosis-related proteins and factors of PI3K/AKT and NF-κB pathways were analyzed by Western blot. Cell viability assay showed that SchA treatment at non-toxic dosages caused a marked enhancement of 5-FU-induced cytotoxicity. Moreover, we explored that miR-195 was up-regulated by SchA; and overexpression of miR-195 reduced cell viability and sensitized 5-FU-resistant HCT116 and SW480 cells to 5-FU. The promoting effect of SchA on 5-FU susceptibility can be partly abolished by miR-195 knockdown. Thus it was speculated that SchA might enhance cell chemosensitivity to 5-FU by up-regulating miR-195. Finally, we found that PI3K/AKT and NF-κB pathways were inhibited by high expression of miR-195 reduced by SchA. Our results suggested that SchA sensitized 5-FU-resistant colon carcinoma cells to 5-FU by up-regulating miR-195. SchA combined with 5-FU could be a promising strategy for the adjuvant chemotherapy of colon cancer.