COX-2抑制剂NS-398对肝癌HepG2细胞凋亡蛋白Bcl-2和Caspase 3表达的影响  

Expression change of apoptosis protein (Bcl-2 and Caspase 3) in HepG2 cell line induced by COX-2 inhibitor NS-398

作　　者：吕必华[1] 张玲[2] 刘静[3] 

机构地区：[1]武汉大学中南医院药学部,430071 [2]武汉科技大学医学院预防医学系 [3]武汉大学药学院

出　　处：《公共卫生与预防医学》2007年第4期21-24,共4页Journal of Public Health and Preventive Medicine

摘　　要：目的探讨选择性环氧合酶2(COX-2)抑制在肝癌HepG2细胞凋亡中的作用。方法用选择性COX-2抑制剂NS-398处理HepG2细胞,流式细胞术测定细胞凋亡和半胱氨酸酶3(Caspase3)活性变化;Western blotting法检测不同浓度NS-398处理后凋亡相关蛋白Bcl-2、Caspase3表达变化。结果流式细胞术显示NS-398(0、100、200、300、400μmol/L)作用HepG2细胞24h后,对照组未见凋亡峰,各试验组(100、200、300、400μmol/L)出现明显的凋亡峰,其凋亡率分别为(10.51±1.04)%、(27.79±2.40)%、(45.72±3.32)%、(60.22±2.03)%,呈明显剂量依赖性(P<0.01),不同浓度NS-398处理后Bcl-2表达下降,Caspase3表达增加,随着NS-398处理浓度的增加,表达活性Caspase3的细胞百分率分别为(2.67±0.22)%、(9.53±0.15)%、(21.28±0.43)%、(39.63±0.8)%、(63.40±0.69)%,呈明显剂量依赖性(P<0.01)。结论选择性COX-2抑制剂NS-398可能通过下调Bcl-2蛋白表达活化Caspase3,从而诱导肝癌细胞HepG2凋亡,COX-2抑制也许可作为新的肝癌的治疗方法。Objective To investigate the possible role of selective cyclooxygenase 2 on the inhibition of induced apoptosis by liver tmnor HepG2 cell llne. Methods HepG2 cell was treated by selective COX-2 inhibitor NS- 398. Cell apoptosis was determined by flowcytometry analysis using PI staining. The expression of Bcl-2 and caspase3 protein was detected by Western blotting. Caspase3 activity was evaluated by active Caspase3 apoptosis kit with flow cytometry. Results Selective COX-2 inhibitor NS-398 stimulated apoptosis in liver tmnor HepG2 cell line significandy. Flowcytometry revealed the apoptotic rate with different concentrations of NS-398 （0,100,200,300,400p.mol/ L） ,the result was （10.51 ±1.04）% ,（27.79 ±2.40）% ,（45.72 ±3.32）% ,（60.22 ±2.03）% respectively. The apoptotic peak did not appear in the control group, which showed a dose-dependent manner（P 〈 0.01 ）. The expression of caspase3 protein was up-regulated while Bcl-2 protein was down-regulated , and the percentage of the ceils with active Caspase3 was（2. 67 ±0.22）%, （9.53 ±0. 15）%, （21.28 ±0.43）%, （39. 63 ±0.8）%, （63.40 ±0.69） %, showing a dose-dependent manner（P 〈 0.01 ）. Conclusion Selective COX-2 inhibitor NS-398 may activate Caspase3 by down-regulating the expression of Bcl-2 protein ,which causes apoptosis of HepG2 cells. Selective COX-2 inhibition may be a novel therapeutics of liver cancer.

关 键 词：环氧化酶2 凋亡 CASPASE3 Bcl-2 HepG2 

分 类 号：R-33[医药卫生] R735.7