CAJ | 학술논문

目的研究PI3K/Akt/mdm2信号通路活化对胃癌细胞阿霉素(DOX)敏感性的影响.方法分别用DOX和PI3K特异性抑制剂wortmannin处理胃癌细胞株SGC7901,采用流式细胞仪检测肿瘤细胞的凋亡,免疫沉淀法检测PI3K活性,Western blot法检测PI3K-p85、phospho-Akt(S473)、phospho-mdm2(S166)、Akt和p53的表达.结果 DOX能诱导胃癌细胞SGC7901凋亡,且凋亡率与作用时间密切相关,联合应用wortmannin后,可促进胃癌细胞凋亡.DOX作用SGC7901细胞3、6、12和24 h后, PI3K活性逐渐增强,分别为(8.4±1.7)%、(12.7±2.1)%、(17.4±3.2)%和(16.8±2.4)%;同时,还促进Akt、mdm2磷酸化和p53表达.wortmannin可以抑制mdm2磷酸化,进一步增强p53的表达.结论 DOX可以诱导PI3K/Akt通路异常激活,并通过促进mdm2磷酸化降低胃癌细胞化疗敏感性.
목적 연구PI3K/Akt/mdm2신호통로활화대위암세포아매소(DOX)민감성적영향.방법 분별용DOX화PI3K특이성억제제wortmannin처리위암세포주SGC7901,채용류식세포의검측종류세포적조망,면역침정법검측PI3K활성,Western blot법검측PI3K-p85、phospho-Akt(S473)、phospho-mdm2(S166)、Akt화p53적표체.결과 DOX능유도위암세포SGC7901조망,차조망솔여작용시간밀절상관,연합응용wortmannin후,가촉진위암세포조망.DOX작용SGC7901세포3、6、12화24 h후, PI3K활성축점증강,분별위(8.4±1.7)%、(12.7±2.1)%、(17.4±3.2)%화(16.8±2.4)%;동시,환촉진Akt、mdm2린산화화p53표체.wortmannin가이억제mdm2린산화,진일보증강p53적표체.결론 DOX가이유도PI3K/Akt통로이상격활,병통과촉진mdm2린산화강저위암세포화료민감성.
Objective To explore whether PI3K/Akt/mdm2 signalling pathway affect the sensitivity of gastric cancer cell line SC, C7901cells to doxorubicin. Methods Gastric cancer cell line SGC7901 cell swere exposed to doxornbiein and specific PI3K inhibitor wortmannin. Cell apoptosis was detected using flow cytometry. PI3K activity was detected by radioactive immunoprecipitation-kinase assay. Western blotting was employed to evaluate the expressions of PI3K-p85, pAkt-S473, Akt, pmdm2-S166 and p53. Results The level of apoptosis in gastric cancer SGC7901 cells treated with doxorubicin was gradually increasing. wortmannin enhanced its effects significantly. PI3K activity and the expression of pAkt-S473 increased in a time-dependent manner, pmdm2-S166, p53 were also increased, wortmannin inhibited phosphorylation of mdm2 and improved the p53 expression. Conclusion PI3K/Akt/mdm2 signalling pathway can be activatedby doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2. PI3K inhibitor wortmannin can enhance sensitivity of gastric cancer cells to chemotherapy.