Effect of Noscapine on Drug Resistance of 5-Fluorouracil-resistant Human Colon Cancer Cell Lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu

Abstract

Objective To investigate the effect of Noscapine(Nos) on drug resistance of 5-Fu-resistant human colon cancer cell lines and its mechanism. Methods Drug-resistant cell lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu were established. MTT assay was used to test IC50 and cell morphology was observed. Cell cycle and apoptosis were determined by flow cytometry. RT-qPCR and Western blot were used to detect the expression and phosphorylation of P38 and the expression of drug resistance-related proteins. Results The drug-resistant cell lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu were successfully constructed. Compared with control group, cell cycle of colon cancer drug-resistant cell lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu after Nos intervention was significantly blocked at G0/G1 phase (P < 0.01), the apoptosis rate was increased, the expression of P38 and phosphorylation were significantly inhibited (P < 0.01), and the expression of MRP, LRP and P-glycoprotein were significantly decreased (P < 0.01). Conclusion Noscapine has a certain toxic effect on 5-Fu-resistant human colon cancer cells and reduces drug resistance. The mechanism may be related to the inhibition of P38 expression and phosphorylation.

Keywords

• noscapine
• colon cancer
• drug resistant cell
• p38
• resistance-related protein