Inhibition of gastric cancer cell growth in vivo by overexpression of adeno-associated virus-mediated survivin mutant C84A

摘要

Survivin is overexpressed in most of human cancer cells and tissues. Its overexpression is associated with apoptosis inhibition, drug resistance, and poor prognosis. In this study, we investigated the effect of adeno-associated virus (AAV)-mediated survivin mutant Cys84Ala [rAAV-Sur-Mut(C84A)] on gastric cancer growth. Sur-Mut(C84A) was subcloned into the AAV expression vector pAM/CAG to generate recombinant (r)AAV-Sur-Mut(C84A) virus. Cell survival was determined by the MTT method. Apoptosis was measured by FACS analysis and TUNEL. Tumor growth was assessed using a xenograft mouse model. Results showed that treatment of rAAV-Sur-Mut(C84A) virus significantly reduced cell survival, induced apoptosis, and sensitized gastric cancer cells to 5-fluorouracil in vitro. Furthermore, treatment of rAAV-Sur-Mut(C84A) virus markedly induced apoptosis and inhibited gastric cancer growth in vivo. Moreover, rAAV-Sur-Mut(C84A) treatment strongly enhanced the antitumor activity of 5-fluorouracil. Our results suggest that the combination of rAAV-Sur-Mut(C84A) with chemotherapy may be a promising strategy for gastric cancer therapy.