研究携带p16基因的增殖缺陷型腺病毒载体对裸鼠皮下胃癌细胞移植瘤的抗肿瘤活性。方法: PCR扩增p16 cDNA，构建腺病毒载体pSuCMVp16表达质粒，在293细胞内重组增殖缺陷型腺病毒AdCMVp16；建立胃腺癌细胞SGC7901皮下移植瘤裸鼠模型，分为3组（AdCMVp16组、AdLacZ组、空白对照组），以2×10 8 pfu/100 μl的重组腺病毒AdCMVp16直接瘤内多点注射，隔日1次，共5次，空白对照组以等量病毒保存液注射，定时测量瘤体生长情况，并以p16免疫组化、TUNEL凋亡检测等观察AdCMVp16抗肿瘤的疗效。结果: 携带p16 基因的增殖缺陷型腺病毒AdCMVp16对胃腺癌裸鼠移植瘤有明显的抑制作用，抑瘤率为58.12%，而对照病毒AdLacZ对胃癌移植瘤的抑瘤率仅为4.26%；病理学检查显示，病毒治疗的癌组织中细胞坏死以凋亡为主，癌细胞中检测到p16基因的表达。结论: 携带p16基因的增殖缺陷型腺病毒能恢复胃癌细胞中p16基因的表达，对胃癌移植瘤生长有明显的抑制作用。

To construct a replicationdeficient adenovirus carrying p16 gene and to investigate its antitumor activity on human gastric cancer xenografts in nude mice. Methods: p16 cDNA was amplified by PCR and was inserted into the plasmid pSuCMV, the latter was then used to recombine the replicationdeficient adenovirus AdCMVp16 in 293 cells. Human SGC7901 gastric cancer xenograft models were established in nude mice and were divided into 3 groups: AdCMVp16, AdLacZ, and control groups. Mice in AdCMVp16 group received intratumoral injections of 2×10 8 pfu/100 l AdCMVp16 ( injected every other day for 5 times). Mice in control group received the same volume of virus preserving solution. The tumor volumes were measured at predefined time points. The antitumor effect of AdCMVp16 was observed by p16 immunochemical study and TUNEL detection of cell apoptosis. Results:The replicationdeficient adenovirus expressing p16 gene evidently inhibited the growth of human gastric cancer xenografts in nude mice (P<0.01), with the inhibition rate being 58.12%; but AdLacZ showed no obvious effect on the growth of xenografts (P>0.05), only with a inhibition rate of 4.26%. The pathological examination showed that apoptoses were the main changes in AdCMVp16 group, and p16 gene was found in the cancer cells. Conclusion: The replicationdeficient adenovirus harboring p16 gene can recover the expression of p16 in gastric cancer cells and subsequently inhibit the growth of human gastric cancer.

R730.53

国家自然科学基金资助项目（No. 30572149）