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 adenocarcinoma SPC-A1 cells was observed by H-E staining. The expressions of Bax, caspase-3, Bcl-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 synergetic effect (Q=1.22). Immunohistochemistry results showed that Ad-ING4 combined with radiotherapy could obviously up-regulate the expressions of Bax, caspase-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.

国家自然科学基金资助项目(No. 81001016)；江苏省卫生厅医学科研基金资助项目(No．H200914)