Ad-ING4联合放疗抑制肺腺癌SPC-A1细胞移植瘤的生长

Ad-ING4 combined with radiotherapy suppresses growth of SPC-A1 cell-transplanted lung adenocarcinoma

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 anticancer effect of adenovirus-mediated inhibitor of growth family 4 （Ad-ING4） combined with radiotherapy on SPC-A1 transplanted lung adenocarcinoma. Methods： SPC-A1 tumor-bearing mice were established and anticancer experiment was conducted on these mice after being randomly divided into 5 groups： PBS group, Ad group, Ad-ING4 group, radiotherapy group and Ad-ING4 combined with radiotherapy group. Tumor growth was recorded by volume. All tumors were taken out and weighed at 15 days after treatment. The morphology of lung adenocar- cinoma SPC-A1 cells was observed by H-E staining. The expressions of Bax, easpase-3, Bel-2, and VEGF were detected by immunohistochemisty. Results： The tumor volume of the Ad-ING4 combined with radiotherapy group was much smaller than that of the Ad-ING4 group and the single radiotherapy group （ [ 743.84 ± 109.06 ] mm3 vs [ 1136.03 ±151.58 ] mm3, [ 1035.67 ± 86.27 ] mm3, P 〈 0.01 ）. The anticancer rate of the Ad-ING4 combined with radiotherapy group was also much better than that of the Ad-ING4 group and the single radiotherapy group （69.62% vs 33.17% vs 35.41% , P 〈 0. 01 ）, which showed an enhanced radiosensitivity and a synergetie effect （ Q = 1.22 ）. Immunohistochemistry results showed that Ad-ING4 combined with radiotherapy could obviously up-regulate the exoressions of Bax, casoase-3 and down-regulate the expressions of Bcl-2 and VEGF. And the effect of the combined group was better than the single Ad-ING4 or radiotherapy group （P 〈 0.01 ）. Conclusion： Ad-ING4 combined with radiotherapy can effectively inhibit the growth of SPC-A1 cell-transplanted lung adenocarcinoma.