抑制膜联蛋白A2表达对人胃癌细胞株裸鼠移植瘤生长的影响及机制

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[目的]通过体内研究探讨膜联蛋白A2(ANXA2)对胃癌生长的影响及相关作用机制。[方法]常规培养人胃癌细胞株BGC-823;将细胞接种到裸鼠皮下制备移植瘤模型。制模成功后随机分组,分别以脂质体/ANXA2-siRNA复合物(实验组)、脂质体/Non-siRNA复合物(对照组)或生理盐水(空白组)分别在各组肿瘤局部注射,每4d干预1次。干预4次后处死,绘制肿瘤生长曲线并比较瘤重。应用荧光定量RT-PCR及免疫组化技术检测各组ANXA2、增殖细胞核抗原(PCNA)、p27m RNA和蛋白表达。[结果]裸鼠皮下移植瘤造模成功率100.00%(15/15)。实验组肿瘤生长比其他两组缓慢,最终体积实验组为(1680.26±110.51)mm3,对照组为(2194.18±188.48)mm3,空白组(2172.37±212.36)mm3(F=9.341,P=0.004);肿瘤重量实验组(20.63±0.46)g,对照组为(22.92±0.86)g,空白组为(23.44±0.90)g(F=11.688,P=0.002)。PCR及免疫组化结果显示实验组ANXA2、PCNAm RNA和蛋白表达明显低于其他两组(P<0.05),而p27m RNA和蛋白表达明显高于其他两组(P<0.01)。[结论 ]抑制ANXA2基因表达后胃癌移植瘤的生长明显受到抑制,这可能与ANXA2基因调控PCNA、p27表达有关。 [Objective] To investigate the effect of annexin A2 (ANXA2) on the growth of gastric cancer and its related mechanism through in vivo study. [Method] The human gastric cancer cell line BGC-823 was routinely cultured. The cells were inoculated subcutaneously in nude mice to prepare the xenografted tumor model. The rats were randomly divided into groups according to the model of liposome / ANXA2-siRNA complex (experimental group), liposome / non-siRNA complex (control group) or normal saline (blank group) , Every 4d intervention 1 times. After intervention 4 times, sacrifice, draw tumor growth curve and compare the tumor weight. The expression of ANXA2, PCNA, p27mRNA and protein in each group were detected by real-time RT-PCR and immunohistochemistry. [Results] The successful rate of subcutaneous tumor implantation in nude mice was 100.00% (15/15). The tumor growth in the experimental group was slower than that in the other two groups. The final volume of the experimental group was (1680.26 ± 110.51) mm3, that of the control group was (2194.18 ± 188.48) mm3, that of the blank group was 2172.37 ± 212.36 mm3 (F = 9.341, P = 0.004) The tumor weight was (20.63 ± 0.46) g in the control group, (22.92 ± 0.86) g in the control group and (23.44 ± 0.90) g in the blank group (F = 11.688, P = 0.002). The results of PCR and immunohistochemistry showed that the mRNA and protein expressions of ANXA2 and PCNA in experimental group were significantly lower than those in the other two groups (P <0.05), while the expression of p27 mRNA and protein was significantly higher than those in the other two groups (P <0.01). [Conclusion] The inhibition of ANXA2 gene expression in gastric cancer xenografts significantly inhibited the growth, which may be related to the regulation of ANXA2 gene PCNA, p27 expression.
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