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15d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(1136.03±151.58)mm3、单纯放疗组为(1035.67±86.27)mm3、Ad—ING4+放疗组为(743.84-4-109.06)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%粥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.