四硫化四砷通过磷酸肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白通路对乳腺癌细胞生长的抑制作用  

The research of As4S4 inhibit the growth of breast cancer cell by regulating phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signal pathway

作　　者：白睿敏[1] 苏静[1] 李孟圈[1] 

机构地区：[1]郑州大学第一附属医院外科医学部乳腺外科,450052

出　　处：《中华实验外科杂志》2017年第7期1142-1144,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察四硫化四砷（As4S4）通过磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路对乳腺癌MCF-7细胞生长的抑制作用。方法利用噻唑蓝（MTT）法分别检测0、20、40、60、80 μmol/L的As4S4处理24、48、72 h及10 μmol/L LY294002处理48 h后MCF-7细胞的增殖；细胞划痕实验及Transwell实验检测As4S4处理48 h对MCF-7细胞迁移及侵袭的影响；流式细胞仪检测As4S4及10 μmol/L LY294002处理48 h对MCF-7细胞凋亡的影响；Western blot检测As4S4及10 μmol/L LY294002处理48 h对MCF-7细胞PI3K/Akt/mTOR通路相关蛋白PI3K、磷酸化蛋白激酶B（p-Akt）、mTOR表达的影响。结果与0 μmol/L处理比较，20 μmol/L As4S4处理24 h时对细胞增殖无明显抑制（P=0.065），处理48、72 h时对细胞增殖具有明显抑制作用（P=0.033），抑制率分别达到11.1%和14.3%。As4S4浓度为40、60、80 μmol/L时对MCF-7细胞增殖具有明显抑制作用（P=0.002），处理72 h后，抑制率分别达到47.9%、58.8%、67.1%。As4S4的抑制作用与时间、浓度呈正相关。和对照组比较，60 μmol/L As4S4作用48 h后，MCF-7细胞迁移及侵袭能力下降42.4%，差异有统计学意义（P=0.005）；细胞的凋亡率增加至（19.56±1.12）%，差异有统计学意义（P=0.009），PI3K的表达无明显变化，p-Akt的表达显著下降64.3%，mTOR的表达显著下降58.7%（P=0.008）。As4S4处理后MCF-7的增殖与凋亡与抑制剂LY294002处理结果一致。结论As4S4可能通过抑制PI3K/Akt/mTOR信号通路抑制乳腺癌MCF-7细胞的增殖及转移，促进细胞凋亡。Objective To investigate the effect of As4S4 inhibit the growth of breast cancer cell by regulating phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signal pathway.Methods Methyl thiazol tetrazolium （MTT） assay was used to detect breast cancer cell MCF-7 proliferation after 0, 20, 40, 60, 80 μmol/L As4S4 treatment for 24, 48, 72 h, and 10 μmol/L LY294002 treatment 48 h. Wound healing and transwell were used to detect the distance of MCF-7 cell migration and invasion after As4S4 dealing with 48 h. Flow cytometry was used to detect MCF-7 cell apoptosis after and 10 μmol/L LY294002 treatment 48 h. Western blotting was used to detect PI3K, p-Akt, mTOR expression levels in MCF-7 cell after As4S4 and 10 μmol/L LY294002 dealing with 48 h.Results Compared with 0 μmol/L treatment, 20 μmol/L As4S4 had no significant inhibition of cell proliferation at 24 h （P=0.065）, it had a significant inhibition of cell proliferation at 48 h and 72 h （P=0.033） with the inhibition ratio of 11.1% and14.3%, respectively.40, 60, 80 μmol/L As4S4 treatment had the most obvious inhibitory effect at 72 h （P=0.002） the inhibition ratio of 47.9%, 58.8%, 67.1%, respectively. After60 As4S4 treatment for 48 h, the migration rate and invasion ability of MCF-7 cell were lower than the control group （with decrease of 42.4%）, the difference was significant （P=0.005）, the apptosis rate was significant increased to （19.56±1.12）% （P=0.009）, the expression of PI3K in MCF-7 cell had no significantly change and p-Akt, mTOR were significantly decreased than control group （P=0.008） with the decrease of 64.3% and 58.7%, respectively. The results of proliferation and apoptosis was consistent with the LY294002 treatment.Conclusion As4S4 may inhibit breast cancer MCF-7 cell proliferation and metastasis and promote apoptosis by inhibiting PI3K/Akt/mTOR signaling pathway.

关 键 词：四硫化四砷 乳腺癌 增殖 转移 凋亡 

分 类 号：R737.9[医药卫生—肿瘤]