Abstract
Atorvastatin (ATO), one of the most common cholesterol reduction agents, exhibits anti-neoplastic effects in several human cancers. However, the antitumor effects of ATO on cervical cancer have not been extensively reported. Recently, autophagy inhibitors are reported to enhance the efficacy of chemotherapeutics. Here, we showed that ATO reduced cell viability and promoted apoptosis of cervical cancer cells by inducing caspase-3 and PARP activation and upregulating Bim. Treatment of ATO also suppressed tumor growth in vivo. In addition, co-culture with GGPP almost completely reversed the morphological change and apoptosis induced by ATO in cervical cancer cells. Furthermore, ATO induced cellular autophagy in cervical cancer cells, which was confirmed by an increase of LC3-I into LC3-II conversion, downregulation of p62 expression, regulation of AMPK and Akt/mTOR pathways. Moreover, pharmacologic inhibition of autophagy using either Baf-A1 or 3-MA significantly enhanced ATO-mediated apoptosis on cervical cancer cells. In conclusion, combination of ATO with autophagy inhibitors could emerge as a new therapeutic strategy for cervical cancer treatment.