【摘要】 目的 觀察已構(gòu)建的含胸苷激酶（TK）自殺基因的重組腺病毒（ADV-TK）對肝癌細胞的體外殺傷作用和對肝癌裸鼠移植瘤的治療效果。 方法 將ADV-TK體外感染人肝癌細胞株SMMC-7721，噻唑藍（MTT）法檢測受感染的SMMC-7721細胞被不同濃度更昔洛韋（GCV）作用后的細胞存活率情況。構(gòu)建肝癌SMMC-7721裸鼠移植瘤模型，觀察腫瘤注射重組腺病毒ADV-TK結(jié)合GCV治療移植瘤的變化。 結(jié)果 相同滴度的重組腺病毒與不同濃度的GCV作用于肝癌細胞株SMMC-7721后，MTT法檢測到細胞的存活率隨著GCV濃度的增加而不斷降低。動物實驗中ADV-TK治療組腫瘤體積明顯小于對照組（ADV-null及NS）（P lt;0.01）。 結(jié)論 重組腺病毒ADV-TK對肝癌SMMC-7721細胞的體外增殖和裸鼠體內(nèi)的移植瘤生長均有明顯的抑制作用。
【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.
引用本文： 陳耿臻,韓慧,許銘炎,鄧小玲. 重組腺病毒ADV-TK對肝癌抑制作用的實驗研究. 華西醫(yī)學, 2010, 25(11): 1941-1943. doi: 復制
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- 2. 陳詩書, 戴冰冰. 基因治療的研究現(xiàn)狀與評價[J]. 中華腫瘤雜志, 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.