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目的本研究旨在观察磷脂酰肌醇3-激酶(PI3K)抑制剂LY294002联合含PTEN基因的重组腺病毒(Ad-PTEN)对人脑胶质瘤裸鼠移植瘤的抗肿瘤作用,初步探讨其可能的作用机制。方法将实验动物24只随机分为4组,即胶质瘤模型给予DMSO对照组、空载对照组、LY294002治疗组及LY294002与Ad-PTEN联合治疗组。皮下接种LN229人脑胶质瘤细胞建立胶质瘤裸鼠皮下移植瘤模型,定期测量动物体质量及肿瘤直径;应用免疫组化法检测肿瘤细胞的PTEN、p-Akt、PCNA、CyclinD1、Caspase-3、MMP-2、p-FAK的表达水平。结果联合治疗组对人脑胶质瘤裸鼠移植瘤抑制作用较对照组及LY294002治疗组均明显增强(均P<0.01);与对照组及LY294002治疗组比较联合治疗组Caspase-3、PTEN表达显著升高(均P<0.05),p-Akt、CyclinD1、MMP2、p-FAK的表达均显著下降(均P<0.05)。结论LY294002与Ad-PTEN联合治疗可以提高对裸鼠移植人脑胶质瘤的抑制作用。
ObjectiveTo study the antitumor effect of phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 combined with PTEN gene recombinant adenovirus (Ad-PTEN) on human glioma xenografts in nude mice. Possible mechanism of action. Methods Twenty-four experimental animals were randomly divided into 4 groups. The glioma model was administered DMSO control group, LY294002 treatment group and LY294002 combined with Ad-PTEN treatment group. The subcutaneously inoculated LN229 human glioma cells were used to establish the subcutaneous xenograft model of glioma in nude mice. The body weight and tumor diameter were measured regularly. The expressions of PTEN, p-Akt, PCNA, CyclinD1, Caspase- 3, MMP-2, p-FAK expression levels. Results Compared with the control group and the LY294002 group, the inhibitory effect of the combined treatment group on the transplanted human glioma xenografts was significantly increased (all P <0.01); compared with the control group and the LY294002 treatment group, the expression of Caspase-3 and PTEN (All P <0.05). The expressions of p-Akt, CyclinD1, MMP2 and p-FAK were significantly decreased (all P <0.05). Conclusion The combination of LY294002 and Ad-PTEN can improve the inhibitory effect on human glioma in nude mice.