ERas Enhances Resistance to CPT-11 in Gastric Cancer

作者：Kubota Eiji; Kataoka Hiromi^*; Tanaka Mamoru; Okamoto Yasuyuki; Ebi Masahide; Hirata Yoshikazu; Murakami Kenji; Mizoshita Tsutomu; Shimura Takaya; Mori Yoshinori; Tanida Satoshi; Kamiya Takeshi; Aoyama Mineyoshi; Asai Kiyofumi; Joh Takashi

来源：Anticancer Research, 2011, 31(10): 3353-3360.

• ERas
• gastric cancer
• chemotherapy
• CPT-11
• rapamycin

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)-kappa B 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 beta mTOR pathway and NF-kappa B, and consequently results in up-regulation of ABCG2.

• 出版日期2011-10