Background/aim: We have reported that embryonic stem cell-expressed Ras (ERas) is expressed in human gastric cancer and is associated with its tumorigenicity. Here, we asked whether ERas plays a role in resistance to chemotherapy in gastric cancer.
Materials and methods: To assess the cytotoxicity of chemotherapeutic agents, ERas-overexpressing human gastric cancer GCIY cells were exposed to anticancer agents, including CPT-11 and inhibitor of mammalian target of rapamycin (mTOR). We also investigated the mechanisms by which ERas induces chemoresistance.
Results: ERas-overexpressing clones were significantly more resistant to CPT-11 than were the control (p<0.001). Administration of rapamycin was significantly cytotoxic to the ERas-overexpressing clones compared with the control (p<0.01). Electrophoresis mobility shift assay revealed that ERas enhanced nuclear factor (NF)-κB activity. PCR array demonstrated that ERas up-regulated several multidrug efflux transporter genes, including ABCG2.
Conclusion: ERas induces chemoresistance to CPT-11 via activation of phosphatidylinositol-3 kinase-protein kinase β mTOR pathway and NF-κB, and consequently results in up-regulation of ABCG2.