呫吨酮并吡啶衍生物XP-15联合紫杉醇对耐药肝癌细胞QGY-7701的体外抑制作用
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摘要
目的:探索呫吨酮并吡啶衍生物XP-15联合紫杉醇对人肝癌QGY-7701耐药细胞株的体外抗肿瘤作用。方法:运用CCK8法、Transwell实验和流式细胞仪检测凋亡技术观察细胞功能学变化,运用Western Blot蛋白免疫印迹技术探索其可能的作用机制。结果:XP-15可明显增强紫杉醇对耐药QGY-7701细胞的抑制作用,XP-15联合紫杉醇作用于耐药QGY-7701细胞24 h后,QGY-7701细胞活力明显减弱,且其侵袭迁移能力明显降低,同时流式细胞仪凋亡检测提示细胞凋亡百分比明显增加。Western Blot蛋白免疫印迹亦证实细胞抗凋亡蛋白bcl-2表达明显降低,肝癌增殖分化相关PI3K及AKT蛋白分子表达减少。结论:XP-15具有增敏紫杉醇诱导耐药QGY-7701细胞凋亡同时抑制其增殖活力的作用,其作用机制可能与下调PI3K-AKT通路活性,同时减少bcl-2抑制凋亡蛋白表达相关。
Objective:To observe the antiproliferative effect of a new xanthono-pyridine derivative(XP-15) combined with taxinol on human hepatocellular carcinoma QGY-7701,which with multi-drug resistance.Methods:CCK8 assay,Transwell experiment and flow cytometry were applied to observe the change of cell function.Western Blot were employed to investigate its possible action mechanism.Results:The results showed that XP-15 enhance the antiproliferative ability of taxinol to QGY-7701,also the combination reduced metastasis of the cell and promoted the apoptosis.Through Western Blot we found out that the level of anti-apoptosis protein bcl-2 were down-regulated and the expression of PI3 K and AKT protein which closely related with proliferation and differentiation of liver cancer were reduced too.Conclusion:We concluded that XP-15 probably sensitize the antitumor effect of taxinol to QGY-7701 through depressing the PI3 K-AKT pathway.
Objective:To observe the antiproliferative effect of a new xanthono-pyridine derivative(XP-15) combined with taxinol on human hepatocellular carcinoma QGY-7701,which with multi-drug resistance.Methods:CCK8 assay,Transwell experiment and flow cytometry were applied to observe the change of cell function.Western Blot were employed to investigate its possible action mechanism.Results:The results showed that XP-15 enhance the antiproliferative ability of taxinol to QGY-7701,also the combination reduced metastasis of the cell and promoted the apoptosis.Through Western Blot we found out that the level of anti-apoptosis protein bcl-2 were down-regulated and the expression of PI3 K and AKT protein which closely related with proliferation and differentiation of liver cancer were reduced too.Conclusion:We concluded that XP-15 probably sensitize the antitumor effect of taxinol to QGY-7701 through depressing the PI3 K-AKT pathway.
引文
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[8] Siddiqui WA,Ahad A,Ahsan H.The mystery of BCL2 family:Bcl-2 proteins and apoptosis:An update[J].Arch Toxicol,2015,89(3):289-317.
[9] Chen Q,Ray S,Hussein M,et al.Role of Apo2L/TRAIL and Bcl-2-family proteins in apoptosis of multiple myeloma[J].Leuk Lymphoma,2003,44(7):1209-1214.
[10] Shu YJ,Weng H,Ye YY,et al.SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway[J].Mol Cancer,2015,14:12.
[11] Zhang Y,Zhang T,Wu C,et al.ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca2+/pI3-kinase/AKT signaling pathway[J].Lab Investig,2017,97:53-69.
[12] Luo M,Liu Q,He M,et al.Gartanin induces cell cycle arrest and autophagy and suppresses migration involving PI3K/Akt/mTOR and MAPK signaling pathway in human glioma cells[J].J Cellular Mol Med,2017,21:46-57.
[13] Xu Chong,Sun GB,Yuan GX,et al.Effects of platycodin D on proliferation,apoptosis and PI3K/AKT signal pathway of human glioma U251 cells[J].Molecules,2014,19(12):21411-21423.
[14] Bai HW,Badaboina S,Park CH,et al.Centipedegrass extract induces apoptosis through the activation of caspases and the downregulation of PI3K/AKT and MAPK phosphorylation in the leukemia cells[J].Int J Mol Med,2015,35(2):511-518.
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[16] Nakanishi K,Sakamoto M,Yasuda J,et al.Critical involvement of the phosphatidylinositol 3-kinase/Akt pathway in anchorage-independent growth and hematogeneous intrahepatic metastasis of liver cancer[J].Cancer Res,2016,62:2971-2975.
[17] Li CW,Xia W,Lim SO,et al.AKT1 inhibits epithelial-to-mesenchymal transition in breast cancer through phosphorylation-dependent Twist1 degradation[J].Cancer Res,2016,76:1451-1462.
[18] Kikuchi L,Chagas AL,Alencar RSSM,et al.Adherence to BCLC recommendations for the treatment of hepatocellular carcinoma:Impact on survival according to stage[J].Clinics(Sao Paulo),2017,72:454-460.