特异性阻断I型磷脂酰肌醇-3激酶信号通路对裸鼠胃癌移植瘤的抑瘤作用  

Effects of class I phosphatidylinositoi-3-kinases inhibitor on gastric cancer cell xenografts in nude mice

作　　者：刘如璐[1] 赵奎[1] 孙家磊[1] 郁立衍[1] 朱宝松[1] 杨晓东[1] 邢春根[1] 

机构地区：[1]苏州大学附属第二医院普通外科,215000

出　　处：《中华胃肠外科杂志》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）

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.

关 键 词：胃肿瘤 磷脂酰肌醇-3激酶 腺病毒 

分 类 号：R735.2[医药卫生—肿瘤]