中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
Chinese Journal of Experimental Surgery
2015年
9期
2143-2145
,共3页
马斌%杨乐%孙刚%董朝%马斌林
馬斌%楊樂%孫剛%董朝%馬斌林
마빈%양악%손강%동조%마빈림
磷酸肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路%LY294002%RAD001%细胞增殖%细胞凋亡
燐痠肌醇3激酶/蛋白激酶B/哺乳動物雷帕黴素靶蛋白信號通路%LY294002%RAD001%細胞增殖%細胞凋亡
린산기순3격매/단백격매B/포유동물뢰파매소파단백신호통로%LY294002%RAD001%세포증식%세포조망
Phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin pathway%LY294002%RAD001%Proliferation%Apoptosis
目的 观察哺乳动物雷帕霉素靶蛋白(mTOR)和磷酸肌醇3激酶(PI3K)特异性抑制剂RAD001和LY294002对人乳腺癌MCF-7、MDA-MB-231细胞株增殖与凋亡的影响,探讨PI3 K/蛋白激酶B (Akt)/mTOR信号通路上下游不同靶点联合阻滞对不同亚型人乳腺癌细胞株的抗肿瘤效应及其机制.方法 体外RAD001和LY294002单独或者联合使用,通过噻唑蓝(MTT)实验计算药物半数抑制剂量(IC50).应用流式细胞仪分析细胞周期分布及凋亡.结果 LY294002和RAD001单药均使能人乳腺癌MCF-7和MDA-MB-231抑制细胞增殖、阻滞周期、诱导细胞凋亡.联合用药后各细胞株的抗肿瘤效应明显增强.结论 针对P13 K/Akt/mTOR信号通路的靶向干预可显著抑制人乳腺癌细胞的增殖,阻滞细胞周期并诱导其凋亡,且通路中不同靶点联合干预的抗肿瘤效应更加显著,尤其是雌激素受体(ER)、孕激素受体(PR)和人类表皮生长因子受体2(Her-2)均阴性的MDA-MB-231细胞株.
目的 觀察哺乳動物雷帕黴素靶蛋白(mTOR)和燐痠肌醇3激酶(PI3K)特異性抑製劑RAD001和LY294002對人乳腺癌MCF-7、MDA-MB-231細胞株增殖與凋亡的影響,探討PI3 K/蛋白激酶B (Akt)/mTOR信號通路上下遊不同靶點聯閤阻滯對不同亞型人乳腺癌細胞株的抗腫瘤效應及其機製.方法 體外RAD001和LY294002單獨或者聯閤使用,通過噻唑藍(MTT)實驗計算藥物半數抑製劑量(IC50).應用流式細胞儀分析細胞週期分佈及凋亡.結果 LY294002和RAD001單藥均使能人乳腺癌MCF-7和MDA-MB-231抑製細胞增殖、阻滯週期、誘導細胞凋亡.聯閤用藥後各細胞株的抗腫瘤效應明顯增彊.結論 針對P13 K/Akt/mTOR信號通路的靶嚮榦預可顯著抑製人乳腺癌細胞的增殖,阻滯細胞週期併誘導其凋亡,且通路中不同靶點聯閤榦預的抗腫瘤效應更加顯著,尤其是雌激素受體(ER)、孕激素受體(PR)和人類錶皮生長因子受體2(Her-2)均陰性的MDA-MB-231細胞株.
목적 관찰포유동물뢰파매소파단백(mTOR)화린산기순3격매(PI3K)특이성억제제RAD001화LY294002대인유선암MCF-7、MDA-MB-231세포주증식여조망적영향,탐토PI3 K/단백격매B (Akt)/mTOR신호통로상하유불동파점연합조체대불동아형인유선암세포주적항종류효응급기궤제.방법 체외RAD001화LY294002단독혹자연합사용,통과새서람(MTT)실험계산약물반수억제제량(IC50).응용류식세포의분석세포주기분포급조망.결과 LY294002화RAD001단약균사능인유선암MCF-7화MDA-MB-231억제세포증식、조체주기、유도세포조망.연합용약후각세포주적항종류효응명현증강.결론 침대P13 K/Akt/mTOR신호통로적파향간예가현저억제인유선암세포적증식,조체세포주기병유도기조망,차통로중불동파점연합간예적항종류효응경가현저,우기시자격소수체(ER)、잉격소수체(PR)화인류표피생장인자수체2(Her-2)균음성적MDA-MB-231세포주.
Objective In this study,by using LY294002 and RAD001,the specific inhibitors of phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR),to observe whether the anti-tumor effects on the proliferation,cycle distribution and apoptosis of combined inhibitors were a synergistic effect,and were differences between different molecular characteristics of human breast cancer cells alone and in combination in vitro.Methods Routinely cultured MCF-7 and MDA-MB-231 cells in vitro.Logarithmic phase cells among each cells were selected and divided into the blank control group,LY294002 group,RAD001 group and the combination group.Methyl thiazol tetrazolium (MTT) assay and flow cytometry were used to detect the cell proliferation,cell cycle distribution and cell apoptosis of different groups.Results LY294002 and RAD001 monotherapy were so capable breast cancer MCF-7 and MDA-MB-231 inhibited cell proliferation,cycle arrest,induction of apoptosis.This combination withered after each cell line significantly enhanced anti-tumor effect.Conclusion Targeted therapy on P13K/protein kinase B (Akt)/mTOR pathway could significantly inhibit the proliferation of human breast cancer cell lines by inducing apoptosis and arresting cell cycle distribution.By using a combination of different inhibitors which were targeted on different related genes of this pathway such as PI3K and mTOR,the anti-tumor effects were more significant increasd compared with monotherapy,especially in MDA-MB-231 cell line which were negative with ER,PR and human epidermal growth factor receptor (Her-2).It was important to provide new research ideas for individualized treatment and translational medicine of breast cancer.