二氯乙酸钠对溶瘤腺病毒ZD55-Smac抑制肝癌细胞生长的影响

Suppression Effect of Hepatocellular Carcinoma Cell Growth by Combining Oncolytic Adenovirus ZD55-Smac and DCA

研究了溶瘤腺病毒ZD55-Smac联合小分子药物二氯乙酸钠(DCA)对人肝癌细胞株的体外抑制效果。首先通过PCR及Western blot鉴定病毒构建正确与否及有无野毒污染,再用MTT法分别检测DCA、ZD55、ZD55-Smac以及DCA与病毒联合对肝癌细胞株Huh-7、PLC、SMMC-7721及肝正常细胞QSG-7701生长的抑制作用;通过倒置显微镜观察了DCA、ZD55-Smac以及DCA和ZD55-Smac联合使用对肝癌细胞株PLC及肝正常细胞QSG-7701的细胞形态变化的影响;利用Hoechst33342染色观察了所处理细胞的凋亡形态学变化。结果表明DCA联合ZD55对肝癌细胞株Huh-7、PLC和SMMC-7721的抑制效果相比较单药物治疗或单病毒治疗有显著增加,而DCA联合ZD55-Smac对肝癌细胞的抑制效果比单病毒治疗有所减弱。该研究为进一步探究ZD55-Smac联合药物治疗打下基础。

In this study,the authors research the antitumor effect in hepatocellular carcinoma cells by combining ZD55-Smac with a small molecule dichloroacetate（DCA）.First,PCR and Western blot are used to detect whether virus is correctly constructed or polluted by wild-type virus.Second,MTT assay is used to test the growth inhibition effects of single or combination therapy on Hepatocellular carcinoma cell lines Huh-7,PLC,SMMC-7721 and human normal liver cell line QSG-7701.Third,microscope is used to observe the Morphologic change of PLC and QSG-7701 four days after administration,and then Hoechst 33342 is added after administration in tumor cells PLC,and 48 hours later cells are observed under fluorescent microscope.Results showed that the antitumor efficacy of ZD55 is significantly enhanced in combination with dichloroacetate,while the antitumor efficacy of ZD55-Smac is significantly inhibited in combination with dichloroacetate.These results implies that DCA may be antagonistic to ZD55-Smac when they are used together to inhibit tumor cells.