Reference - Detail
| RRC ID | 57972 |
|---|---|
| Author | Kubota E, Kataoka H, Tanaka M, Okamoto Y, Ebi M, Hirata Y, Murakami K, Mizoshita T, Shimura T, Mori Y, Tanida S, Kamiya T, Aoyama M, Asai K, Joh T. |
| Title | ERas enhances resistance to CPT-11 in gastric cancer. |
| Journal | Anticancer Res |
| Abstract |
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. |
| Volume | 31(10) |
| Pages | 3353-60 |
| Published | 2011-10-1 |
| PII | 31/10/3353 |
| PMID | 21965746 |
| MeSH | Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use Camptothecin / analogs & derivatives* Camptothecin / pharmacology Camptothecin / therapeutic use Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects DNA / metabolism DNA Topoisomerases, Type I / metabolism Drug Resistance, Neoplasm / drug effects Drug Resistance, Neoplasm / genetics Embryonic Stem Cells / drug effects Embryonic Stem Cells / metabolism* Gene Expression Profiling Gene Expression Regulation, Neoplastic / drug effects Humans Inhibitory Concentration 50 Irinotecan Models, Biological NF-kappa B / metabolism Protein Binding / drug effects Sirolimus / pharmacology Stomach Neoplasms / drug therapy* Stomach Neoplasms / genetics Stomach Neoplasms / pathology Up-Regulation / drug effects ras Proteins / metabolism* |
| Resource | |
| Human and Animal Cells | GCIY(RCB0555) |