摘要
目的研究利用重组腺病毒特异性阻断I型磷脂酰肌醇-3激酶（P13K）信号转导通路，对裸鼠胃癌移植瘤的影响，并探讨其相关作用机制。方法用人胃癌细胞SGC7901建立裸鼠胃癌移植瘤模型，分为3组，分别给予重组腺病毒P13K（I）-RNAi-AD、空病毒NC-RNAi-GFP-AD和生理盐水处理。给药后第3、6和9天分别取5只裸鼠处死，测量移植瘤体积，计算抑瘤率；应用免疫组织化学法检测移植瘤组织的TNF-α、环氧化酶2（COX2）、P53、增殖细胞核抗原（PCNA）、E-cadherin及nm23／DNPK的表达水平。结果给药后第3、6和9天，P13K（I）-RNAi-AD组的抑瘤率分别为14.2％，21.0％和28.1％，显著高于空病毒组（1.3％、1.9％和2.0％，均P〈0.05）。给药后第9天。P13K（I）-RNAi-AD组TNF-α、P53、E-eadherin、nm23／DNPK蛋白的表达均明显高于空病毒组和对照组；而COX2、PCNA的表达则明显减少（P〈0.05）。结论重组腺病毒P13K（I）-RNAi-AD对裸鼠胃癌移植瘤有一定的抗肿瘤作用，其机制为通过抑制胃癌细胞增殖、血管生成、降低侵袭能力等多个途径共同发挥抑癌效应。
Objective To investigate the effect of recombinant adenovirus （phosphafidylinositol- 3-kinases（PI3K） （ I ）-RNAi-AD which blocks the class I PI3K signaling pathway on gastric carcinoma cells xenografts in nude mice. Methods Subcutaneous tumor models of nude mice were established with SGC7901 cells and randomly divided into PI3K（ I ）-RNAi-AD group, NC-RNAi-GFP-AD group and control group. The tumor size and the inhibitory rate of tumor growth on days 3, 6, and 9 after cell transplantation were measured. The expression of TNF-α, COX2, P53, PCNA, E-cadherin and nm23/DNPK in tumor tissues were detected by immunohistoehemistry. Results Tumor growth was significantly inhibited in the PI3K（ I ）-RNAi-AD group（ 14.2%, 21.0%, and 28.1%）on days 3, 6, 9 compared with NC-RNAi-GFP-AD group（1.3%, 1.9%, and 2.0%, all P〈0.05）. The expressions of TNF-a, P53, F,-cadherin and nm23/DNPK were up-regulated, and the expressions of COX2 and PCNA were down-regnlated in the PI3K（ I ）-RNAi-AD group by immunohistochemical staining（all P〈0.05）. Conclusions PI3K（ I ）- RNAi-AD can inhibit the growth of SGC7901 cell transplantation tumor in vivo in nude mice by inhibiting cell growth, reducing the capacity of tumor invasion and inhibiting tumor angiogenesis.
出处
《中华胃肠外科杂志》
CAS
CSCD
2013年第5期484-488,共5页
Chinese Journal of Gastrointestinal Surgery
基金
国家自然科学基金（81172348）
江苏省自然科学基金（BK2008168）
江苏省卫生厅基金（H200719）
江苏省高校自然科学基金（08KJB320014）
关键词
胃肿瘤
磷脂酰肌醇-3激酶
腺病毒
Stomach neoplasms
Phosphatidylinositol-3-kinases
Recombinant adenovirus
