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目的:研究腺病毒介导的肿瘤生长抑制因子4(inhibitor of growth family 4,ING4)联合放疗对肺腺癌SPC-A1细胞移植瘤生长的抑制作用。方法:制备SPC-A1细胞荷瘤小鼠模型,随机分为PBS组、Ad组、Ad-ING4组、放疗组、Ad-ING4+放疗组。测量各组荷瘤小鼠移植瘤的体积变化,治疗15 d后摘取瘤块,称质量并计算抑瘤率;H-E染色观察瘤体组织细胞的形态学变化,免疫组化法检测瘤体组织中Bax、caspase-3、Bcl-2、VEGF等因子的表达。结果:治疗后第15天SPC-A1移植瘤体积:Ad-ING4组为(1 136.03±151.58)mm3、单纯放疗组为(1 035.67±86.27)mm3、Ad-ING4+放疗组为(743.84±109.06)mm3,联合组可有效抑制肿瘤生长(P<0.01);此外,联合组抑瘤率也显著高于单纯Ad-ING4组或放疗组(69.62%vs 33.17%、35.41%,P<0.01),呈现放疗增敏协同作用(Q=1.22)。免疫组化结果显示,Ad-ING4及其联合放疗组能明显上调Bax、caspase-3等蛋白的表达,下调Bcl-2、VEGF等蛋白的表达,且Ad-ING4+放疗组对这些蛋白表达的调节作用强于Ad-ING4组、单纯放疗组(P<0.01)。结论:Ad-ING4联合放疗可有效抑制肺腺癌SPC-A1细胞移植瘤的生长。
Objective: To study the inhibitory effect of adenovirus mediated ING4 combined with radiotherapy on the growth of SPC-A1 cells in lung adenocarcinoma. Methods: SPC-A1 cell-bearing mice were randomly divided into PBS group, Ad group, Ad-ING4 group, radiotherapy group and Ad-ING4 + radiotherapy group. The tumor volume of tumor-bearing mice in each group was measured. The tumor mass was removed 15 days after treatment and the tumor inhibition rate was calculated. The morphological changes of tumor cells were observed by HE staining and the tumor tissues were detected by immunohistochemistry In Bax, caspase-3, Bcl-2, VEGF and other factors. Results: On the 15th day after treatment, the volume of SPC-A1 transplanted tumor was (1 136.03 ± 151.58) mm3 in Ad-ING4 group, (1035.67 ± 86.27) mm3 in radiotherapy alone group and 743.84 ± 109.06 in Ad-ING4 + radiotherapy group mm3, the combination group can effectively inhibit tumor growth (P <0.01). In addition, the inhibition rate of the combination group was also significantly higher than that of Ad-ING4 alone group or radiotherapy group (69.62% vs 33.17%, 35.41%, P <0.01) Radiotherapy sensitization synergies (Q = 1.22). The results of immunohistochemistry showed that Ad-ING4 and its combined radiotherapy group could up-regulate the expressions of Bax, caspase-3 and other proteins, down-regulate the expression of Bcl-2 and VEGF, and regulate the expression of these proteins in Ad-ING4 + radiotherapy group Stronger than Ad-ING4 group, radiotherapy alone group (P <0.01). Conclusion: Ad-ING4 combined with radiotherapy can effectively inhibit the growth of SPC-A1 cells in lung adenocarcinoma.