【摘要】 目的 观察已构建的含胸苷激酶（TK）自杀基因的重组腺病毒（ADV-TK）对肝癌细胞的体外杀伤作用和对肝癌裸鼠移植瘤的治疗效果。 方法 将ADV-TK体外感染人肝癌细胞株SMMC-7721，噻唑蓝（MTT）法检测受感染的SMMC-7721细胞被不同浓度更昔洛韦（GCV）作用后的细胞存活率情况。构建肝癌SMMC-7721裸鼠移植瘤模型，观察肿瘤注射重组腺病毒ADV-TK结合GCV治疗移植瘤的变化。 结果 相同滴度的重组腺病毒与不同浓度的GCV作用于肝癌细胞株SMMC-7721后，MTT法检测到细胞的存活率随着GCV浓度的增加而不断降低。动物实验中ADV-TK治疗组肿瘤体积明显小于对照组（ADV-null及NS）（P lt;0.01）。 结论 重组腺病毒ADV-TK对肝癌SMMC-7721细胞的体外增殖和裸鼠体内的移植瘤生长均有明显的抑制作用。
【Abstract】 Objective To explore the inhibitory effect of recombinant adenovirus containing TK gene (ADV-TK) on transfected human liver cancer cells SMMC-7721 in vitro and murine transplanted hepatocarcinoma in vivo. Methods SMMC-7721 cells transfected with ADV-TK were exposed to medium with GCV. The cell viability was measured by MTT assays. In the established model of SMMC-7721 human liver cancer, nude mice underwent intratumoral injection with 1 109 pfu ADV-TK, the control vector (ADV-null) or normal saline (NS) and again 7 days later, twice for all. GCV was given at a dose of l00 mg/(kg•d) on the following day of injection for 10 days. The tumor inhibitory effect was observed by measuring the tumor sizes. Results After transfected by ADV-TK in vitro, and combined with GCV, the cell growth of SMMC-7721 cell were significantly suppressed. The result of in vivo assay showed that tumor volumes in treatment group were apparently smaller than that in the control group (P lt;0.01). Conclusion Recombinant adenovirus combined with GCV shows a significant inhibitory effect on SMMC-7721 cells in vitro and murine transplanted hepatocarcinoma in vivo.
Citation：
CHEN Gengzhen,HAN Hui,XU Mingyan,DENG Xiaoling. Experimental Study on Gene Therapy for Liver Cancer via Recombinant Adenovirus Containing TK Gene. West China Medical Journal, 2010, 25(11): 1941-1943. doi:
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- 2. 陈诗书, 戴冰冰. 基因治疗的研究现状与评价[J]. 中华肿瘤杂志, 2002, 24(4): 313-315. .
- 3. Portsmouth D, Hlavaty J, Renner M. Suicide genes for cancer therapy [J]. Mol Aspects Med, 2007, 28 (1): 4-41. .
- 4. AltanerC. Prodrug cancer gene therapy[J]. CancerLett, 2008, 270(2): 191-201. .
- 5. Stefani AL, Barzon L, Castagliuolo I, et al. Systemic efficacy of combined suicide/cytokine gene therapy in a murinemodel ofhepatocellular carcinoma[J]. J Hepatol, 2005, 42(5): 728-735. .
- 6. Majumdar AS, Hughes DE, Lichtsteiner SP, et al. The telomerase reverse transcriptase promoter drives efficacious tumor suicide gene therapy while preventing hepatotoxicity encountered with constitutive promoters[J]. Gene Ther, 2001, 8(7): 568-578. .
- 7. Bonini C, Ferrari G, Verzeletti S, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia[J]. Science, 1997, 276(5316): 1719-1724. .
- 8. Zhou JF, Gao QL, Chen G, et al. Novel oncolytic adenovirus selectively targets tumor-associated polo-like kinase 1 and tumor cell viability[J]. Clin Cancer Res, 2005, 11(23): 8431-8440. .
- 9. Aguilar LK, Teh BS, Vlachaki MT, et al. AdV-tk/valacyclovir gene therapy in combination with radiotherapy for prostate cancer: interim results of a phase Ⅰ/Ⅱ clinical trial[J]. Am Soc Clin Oncol, 2002, abstract No: 25.
