Overexpression of AKT decreases the chemosensitivity of gastric cancer cells to cisplatin in vitro and in vivo

Cisplatin (CDDP) is one of the most efficacious and widely used cytotoxic anticancer drugs used for the treatment of numerous types of cancer. However, its efficacy is limited as a result of acquired drug resistance. AKT overexpression may provide a potential mechanism leading to the resistance of human gastric cancer cells; however, the precise mechanism of the development of CDDP drug resistance remains uncertain. In the present study, we demonstrate that CDDP resistance is associated with AKT overexpression at the cellular and molecular level. We also observed that increased expression levels of AKT were sufficient to inhibit the resistance of gastric cancer cells to CDDP and that overexpressed AKT interacted with reactive oxygen species which were generated by CDDP. These results indicate that AKT activity is essential for the regulation of CDDP resistance in gastric cancer cells. Our results further demonstrate that AKT induces gastric cancer cells to become resistant to CDDP through the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Taken together, these data support a potential role for AKT overexpression and the JAK2/STAT3 pathway in the development of CDDP drug resistance in human gastric cancer cells. We hypothesize that AKT may represent a future pharmacological target for the inhibition of CDDP resistance in human cancer.