Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer

Abstract

Cervical cancer still remains a major health problem in women worldwide. Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues and is converted to form the active metabolite SN-38. The study tried to explore the in vitro mechanisms of apoptosis induced by SN-38 in cervical cancer cell lines HeLa and SiHa. The results demonstrated here that SN-38 inhibited cell proliferation in a time- and dose-dependant manner. Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt.