AstragalosideII inhibits autophagic flux and enhance chemosensitivity of cisplatin in human cancer cells.

Abstract

Inhibition of autophagy has been daily served as a promising anti-cancer treatment strategies. AstragalosideII (ASII), a main compound isolated from traditional Chinese medicine Radix Astragali, has been demonstrated to inhibit autophagy and reverse multidrug resistance in human hepatic cancer cells Bel-7402/5-FU. In this study, we inspected the function and mechanisms of ASII and cisplatin on autophagy in human cancer cells, and assessed the effect of ASII on cisplatin-induced apoptosis. We found ASII increased LC3II protein level, p62 protein level and GFP-LC3 puncta accumulation in human cancer cells. Furthermore, we found that ASII downregulated the expression of lysosomal cathepsinB/L (CTSB/L) in EBSS medium and affected the lysosomal acidification. Finally, we demonstrated that cisplatin induced protective autophagy which was involved of PI3K/Akt/mTOR pathway. Moreover, ASII in conjunction with cisplatin significant reduced cell viability, arrested in S phase and increased apoptosis. In conclusion, these findings suggested that ASII served as autophagy inhibitor which restored chemosensitivity of anticancer agent cisplatin and enhanced tumor cell death.