目的:探讨mda7/IL24对裸鼠肝癌细胞移植瘤的生长抑制和促凋亡作用及其相关机制。方法：构建携带mda7基因的重组腺病毒载体Admda7。以HepG2细胞皮下接种建立裸鼠肝癌移植瘤模型，采用瘤内单点注射的方法分别给予AdGFP、Admda7和ALLN（毒胡萝卜素，NAcLLnorleucinal）+Admda7，观察瘤质量和瘤体积的变化，通过免疫组化和TUNEL法检测肿瘤组织内凋亡相关蛋白caspase3活化、细胞增殖相关抗原ki67和微血管密度、细胞凋亡率，并通过Western blotting检测caspase12、caspase3和Bax的表达。结果： Ad.mda7治疗组和Ad.GFP对照组肿瘤体积分别为（312.6±30.2）mm3和（520.6±30.0）mm3（P<0.01），两组的肿瘤质量分别为（0.321±0.031）g和（0.534±0.030）g（P<001）；Ad.mda7治疗后瘤细胞的凋亡率显著高于对照组（P<0.01）；Ad.mda7可抑制肝癌组织ki67表达、微血管密度和促进caspase3的表达。 经 ALLN 处理的裸鼠，明显抑制Ad.mda7对肝癌细胞的致凋亡作用（P<0.05），并且下调Ad.mda7诱导的caspase12、caspase3和Bax的表达。结论： Ad.mda7可显著抑制裸鼠肝癌移植瘤的生长和新生血管的形成，并通过内质网应激通路显著诱导肿瘤细胞的凋亡。

Objective: To study the proliferation inhibition and apoptosis promotion effect of mda7/IL24 in transplanted hepatocellular cancer cells in nude mice, and to study the related mechanism. Methods: Recombinant vector Ad.mda7 was constructed. BALB/c nude mice liver cancer model was established by subcutaneous implanting of HepG2 cells. Nude mice were administered with Ad.GFP, Ad.mda7 or ALLN+Ad.mda7 via intratumor single point injection. The changes of tumor size and weight were observed. Activation of caspase3, apoptosis of cancer cells, cell proliferationassociated antigen ki67 and microvascular density were assessed by immunohistochemistry and TUNEL method. Caspase12, caspase3 and Bax expression was examined via Western blotting. Results: The tumor sizes of Ad.mda7 treated mice and Ad.GFP treated mice were (312.6±30.24) mm3 vs (520.6±30.00) mm3 (P<0.05), and the weights were (0.321±0.031) g vs (0.534±0.030) g, respectively (P<0.05). Ad.mda7 inhibited expression of ki67 and CD31, and induced activation of caspase3 in subcutaneous tumor xenografts. ALLN reversed the apoptosis inducing effect of Ad.mda7 （P<0.05）， downregulated the expression of caspase12, caspase3 and Bax induced by Ad. Mda7. Conclusion: mda7/IL24 can obviously inhibit proliferation and angiogenesis of transplanted hepatocellular cancer cells, and induce apoptosis of hepatocellular cancer cells through activating the endoplasmic reticulum stress pathway.

国家自然科学基金资助项目（No.30873020）