中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
5期
721-725,726
,共6页
FFJ-5%丙酮酸激酶M2%EGFR%Akt%细胞凋亡%细胞耐药性%信号通路
FFJ-5%丙酮痠激酶M2%EGFR%Akt%細胞凋亡%細胞耐藥性%信號通路
FFJ-5%병동산격매M2%EGFR%Akt%세포조망%세포내약성%신호통로
FFJ-5%PKM2%EGFR%Akt%cell apopto-sis%drug resistant cells%cell signal pathway
目的:探讨 FFJ-5对人乳腺癌细胞 MCF7及其耐药细胞 MCF7/DOX 的作用及其机制。方法采用 MTT 法检测FFJ-5对 MCF7及 MCF7/DOX 细胞的增殖抑制作用及其对柔红霉素(doxorubicin,DOX)在耐药细胞 MCF7/DOX 中化疗敏感性的影响;Western blot检测FFJ-5对EGFR、p-EGFR、Akt、p-Akt、PKM2、caspase-3、cleaved caspase-3、PARP、cleaved PARP及P-gp蛋白表达的影响;DNA ladder 分析检测FFJ-5对细胞基因组DNA的影响;RT-PCR检测低剂量 FFJ-5对多药耐药基因MDR1 mRNA水平的影响。结果 FFJ-5抑制了MCF7细胞生长,降低了MCF7细胞中EGFR、Akt 的表达及活性,下调了PKM2水平;FFJ-5可激活caspase-3、促使基因组DNA断裂;同时FFJ-5也能抑制耐药细胞MCF7/DOX生长,并增强 DOX 在MCF7/DOX细胞中的活性,同时降低了MCF7/DOX 细胞中 EGFR、p-EGFR 及 PKM2水平,但对MDR1 mRNA水平无影响。结论 FFJ-5可通过抑制 EGFR-Akt-PKM2通路及激活线粒体凋亡相关因子 caspase-3来抑制MCF7细胞生长,并诱导其凋亡,并可逆转MCF7/DOX的耐药性。
目的:探討 FFJ-5對人乳腺癌細胞 MCF7及其耐藥細胞 MCF7/DOX 的作用及其機製。方法採用 MTT 法檢測FFJ-5對 MCF7及 MCF7/DOX 細胞的增殖抑製作用及其對柔紅黴素(doxorubicin,DOX)在耐藥細胞 MCF7/DOX 中化療敏感性的影響;Western blot檢測FFJ-5對EGFR、p-EGFR、Akt、p-Akt、PKM2、caspase-3、cleaved caspase-3、PARP、cleaved PARP及P-gp蛋白錶達的影響;DNA ladder 分析檢測FFJ-5對細胞基因組DNA的影響;RT-PCR檢測低劑量 FFJ-5對多藥耐藥基因MDR1 mRNA水平的影響。結果 FFJ-5抑製瞭MCF7細胞生長,降低瞭MCF7細胞中EGFR、Akt 的錶達及活性,下調瞭PKM2水平;FFJ-5可激活caspase-3、促使基因組DNA斷裂;同時FFJ-5也能抑製耐藥細胞MCF7/DOX生長,併增彊 DOX 在MCF7/DOX細胞中的活性,同時降低瞭MCF7/DOX 細胞中 EGFR、p-EGFR 及 PKM2水平,但對MDR1 mRNA水平無影響。結論 FFJ-5可通過抑製 EGFR-Akt-PKM2通路及激活線粒體凋亡相關因子 caspase-3來抑製MCF7細胞生長,併誘導其凋亡,併可逆轉MCF7/DOX的耐藥性。
목적:탐토 FFJ-5대인유선암세포 MCF7급기내약세포 MCF7/DOX 적작용급기궤제。방법채용 MTT 법검측FFJ-5대 MCF7급 MCF7/DOX 세포적증식억제작용급기대유홍매소(doxorubicin,DOX)재내약세포 MCF7/DOX 중화료민감성적영향;Western blot검측FFJ-5대EGFR、p-EGFR、Akt、p-Akt、PKM2、caspase-3、cleaved caspase-3、PARP、cleaved PARP급P-gp단백표체적영향;DNA ladder 분석검측FFJ-5대세포기인조DNA적영향;RT-PCR검측저제량 FFJ-5대다약내약기인MDR1 mRNA수평적영향。결과 FFJ-5억제료MCF7세포생장,강저료MCF7세포중EGFR、Akt 적표체급활성,하조료PKM2수평;FFJ-5가격활caspase-3、촉사기인조DNA단렬;동시FFJ-5야능억제내약세포MCF7/DOX생장,병증강 DOX 재MCF7/DOX세포중적활성,동시강저료MCF7/DOX 세포중 EGFR、p-EGFR 급 PKM2수평,단대MDR1 mRNA수평무영향。결론 FFJ-5가통과억제 EGFR-Akt-PKM2통로급격활선립체조망상관인자 caspase-3래억제MCF7세포생장,병유도기조망,병가역전MCF7/DOX적내약성。
Aim To investigate the roles of FFJ-5 in human breast cancer MCF7 cells and drug-resistant MCF7/DOX cells and to explore its mechanisms. Methods MTT assay was used to detect the effect of FFJ-5 on MCF7 and MCF7/DOX cell proliferation and sensitivity of doxorubicin in MCF7/DOX cells.West-ern blot was used to investigate the effect of FFJ-5 on expression of EGFR,p-EGFR,Akt,p-Akt,PKM2, cleaved caspase-3,cleaved PARP and P-gp.DNA lad-der analysis was performed to determine the effect of FFJ-5 on genomic DNA.RT-PCR was performed to de-tect the influence of FFJ-5 on multidrug resistance gene MDR1 mRNA levels.Results The results showed that FFJ-5 inhibited the growth of MCF7 ,inhibited the expression and activity of EGFR and Akt,and conse-quently reduced the expression of PKM2 in MCF7 cells;FFJ-5 activated caspase-3 and induced genomic DNA fragmentation;FFJ-5 also inhibited the growth of MCF7/DOX cells and enhanced the anti-tumor activity of doxorubicin in MCF7/DOX cells.Conclusion The results suggest that FFJ-5 could inhibit MCF7 cell growth and induce MCF7 cell apoptosis through inhibi-tion of EGFR-Akt-PKM2 pathway and activation of ap-optosis-related factors caspase-3 , meanwhile FFJ-5 could also reverse the resistance of MCF7/DOX.