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目的:探讨溶瘤腺病毒(ZD55-gene)作为载体携带外源抗癌基因(XAF1)抗肝癌移植瘤的生长及其安全性。方法:抽提溶瘤腺病毒ZD55-XAF1的基因组DNA,PCR扩增鉴定病毒;细菌平板培养和支原体检测试剂盒检测细胞有无细菌、支原体污染;通过荷瘤小鼠动物实验,观察溶瘤腺病毒ZD55-XAF1对肝癌移植瘤生长的抑制、小鼠的临床反应指标、血清肝毒性指标、各脏器组织中的病毒残留分布及病理切片观察。结果:细胞培养过程无细菌和支原体污染;较对照组,受试小鼠血清肝酶AST活性上升(P<0.05),而ALT和ALP活性基本无变化(P>0.05);PCR检测各脏器均有病毒基因组DNA存在;HE染色显示受试小鼠各脏器具有不同程度的损伤,病毒处理对肿瘤细胞具有明显的杀伤效果,而受试小鼠的临床反应并无明显异常。结论:溶瘤腺病毒ZD55-XAF1能够抑制肿瘤生长,杀死肿瘤细胞,对小鼠血清肝酶活性影响较小而对各脏器有不同程度的轻微损伤,作为癌症基因治疗载体有潜在的应用价值但其安全性还有待提高。
Objective: To investigate the growth and safety of oncolytic adenovirus (ZD55-gene) as a vector carrying XAF1 against liver cancer xenografts. Methods: The genomic DNA of oncolytic adenovirus ZD55-XAF1 was extracted and identified by PCR. Bacterial culture and mycoplasma detection kit were used to detect the presence or absence of bacteria and mycoplasma contamination. The tumor-bearing mice were observed by animal experiments The inhibition of the virus ZD55-XAF1 on the growth of hepatocellular carcinoma, the clinical response index of mice, the index of serum hepatotoxicity, the distribution of virus residues in various organs and pathological sections. Results: There was no bacterial and mycoplasma contamination in the cell culture. Compared with the control group, serum ALT and ALP activity of AST in experimental mice increased (P <0.05), but ALT and ALP activity did not change (P> 0.05) All of the virus genomic DNA existed; HE staining showed that the organs of the mice had different degrees of damage, the virus treatment has obvious killing effect on tumor cells, and the clinical response of the mice showed no obvious abnormalities. Conclusion: Oncolytic adenovirus ZD55-XAF1 can inhibit tumor growth and kill tumor cells. It has little effect on serum liver enzyme activity and slight damage to various organs. It has potential application as cancer gene therapy vector Value but its security needs to be improved.