Molecular therapy with recombinant antisense c-myc adenovirus for human gastric carcinoma cells in vitro and in vivo
Molecular therapy with recombinant antisense c-myc adenovirus for human gastric carcinoma cells in vitro and in vivo
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DOI：
10.1046/j.1440-1746.2001.02361.x
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发表时间：
2001-01-01
影响因子：
4.1
通讯作者：
Wu, M
中科院分区：
文献类型：
--
作者：
Chen, JP;Lin, C;Wu, M
背景和目标：本研究使用重组反义c-myc腺病毒（Ad-ASc-myc）转染人胃癌细胞株SGC 7901，观察c-myc基因表达的改变对胃癌细胞增殖、凋亡及裸鼠移植瘤生长的影响。人胃癌细胞系SGC 7901，采用X-gal染色、MTT、DNA Ladder、TUNEL、流式细胞术、聚合酶链反应和westernblot等方法对Ad-ASc-myc和腺病毒LacZ重组体（Ad-LacZ）处理的细胞进行体外分析。结果：Ad-ASc-myc能明显抑制胃癌细胞株SGC 7901的生长并诱导其凋亡。Ad-ASc-myc感染的胃癌细胞株SGC 7901的增殖抑制率为44.1%。应用DNA Ladder、TUNEL和流式细胞术检测Ad-ASc-myc对胃癌细胞的杀伤作用，发现Ad-ASc-myc对胃癌细胞的杀伤机制为凋亡。Ad-ASc-myc感染裸鼠后7 ~ 30 d内均未形成肿瘤，而Ad-LacZ和亲本SGC 7901细胞感染裸鼠后7 ~ 30 d内未见肿瘤形成。对裸鼠皮下移植性胃癌SGC 7901细胞瘤的实验治疗表明，瘤内滴注Ad-ASc-myc可抑制肿瘤的生长。结论：重组反义c-myc腺病毒在体内外均能抑制胃癌细胞的生长，诱导其凋亡，在胃癌基因治疗中具有潜在的临床应用价值。(C)2001 Blackwell Science Asia Pty Ltd.
Background and Aims: This study used a recombinant antisense c-myc adenovirus (Ad-ASc-myc) to evaluate how alterations of c-myc expression in the SGC7901 human gastric carcinoma cells could influence the proliferation, apoptosis and the growth of human gastric tumors in nude mice.Methods: The human gastric carcinoma cell line, SGC7901, treated with Ad-ASc-myc or adenovirus recombinants carrying LacZ gene (Ad-LacZ) were analyzed by using X-gal stain, MTT, DNA ladder, TUNEL assay, flaw cytometric analysis, polymerase chain reaction and western blot in vitro. The tumorigenicity and experimental therapy in nude mice models were assessed in vivo.Results: The Ad-ASc-myc could strongly inhibit cell growth and induce apoptosis in SGC7901 cells. The proliferation of the Ad-ASc-myc-infected SGC7901 cells was reduced by 44.1%. The mechanism of killing gastric carcinoma cells by Ad-ASc-myc was found to be apoptosis, which was detected by the use of a DNA ladder, TUNEL and flow cytometric analysis. Infection of Ad-ASc-myc in nude mice showed that all three mice failed to form tumors from the 7 to 30 day period, compared with injection of Ad-LacZ and parent SGC7901 cells. Experimental therapy on the nude mice bearing subcutaneous tumors of SGC7901 cells showed that intratumor instillation of Ad-ASc-myc inhibited the growth of the turners. Recombinant antisense c-myc adenovirus-treated tumors were inhibited by 68.9%, compared with tumors injected with Ad-LacZ and control (LacZ and phosphate-buffered saline).Conclusion: The expression of Ad-ASc-myc can inhibit growth and induce apoptosis of gastric cancer cells in vitro and in vivo and thus is a potential clinical utility in gene therapy for the treatment of gastric carcinoma. (C) 2001 Blackwell Science Asia Pty Ltd.