RESUMO
Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development.
Assuntos
Proliferação de Células/fisiologia , Replicação do DNA/fisiologia , MicroRNAs/fisiologia , Proteína de Replicação A/metabolismo , Apoptose/genética , Apoptose/fisiologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Ciclo Celular/genética , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Senescência Celular/genética , Senescência Celular/fisiologia , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Ensaio Cometa , Replicação do DNA/genética , Histonas/metabolismo , Humanos , Imuno-Histoquímica , MicroRNAs/genética , MicroRNAs/metabolismo , Interferência de RNA/fisiologia , Proteína de Replicação A/genéticaRESUMO
Multi-drug resistance (MDR) cancer is an intractable problem. Over-expression of drug efflux transporters such as ABCB1, ABCC1 and ABCG2 contributes to it, by which they pump drugs out of cells, and result in the decrease in the efficacy of chemotherapy. To reverse the cancer MDR, we used 3-methyladenine (3-MA) treatment on taxol or doxorubicin stressed MDR cell lines A2780DX5 and SGC7091R and xeno-tumor implanted mice. The results indicate that ABCB1, ABCC1 and ABCG2 were depressed, and the PI3K-AKT-mTOR pathway was blocked. Moreover, using FITC-labeled taxol as the indicator, we observed that the drug accumulation was enhanced in MDR cells and more cells were killed after 3-MA administration. Thus suggesting that 3-MA can reverse cancer MDR via depressing agent-efflux transporters.
