携带mda-7基因的腺病毒联合达卡巴嗪对人黑素瘤裸鼠移植瘤生长的抑制作用

Inhibitory effect of adenovirus carrying melanoma differentiation- associated gene - 7 in combination with dacarbazine on growth of human malignant melanoma in nude mice

目的:评价携带mda-7基因的腺病毒(Ad·mda-7)与达卡巴嗪(DTIC)联合应用对人恶性黑素瘤裸鼠移植瘤的抑制作用。方法:建立裸鼠恶性黑素瘤移植瘤模型,分别给予PBS、Ad·mda-7、DTIC或Ad·mda-7联合DTIC治疗后,测量肿瘤生长体积。免疫印迹法检测MDA-7蛋白表达,TUNEL法检测肿瘤组织凋亡,免疫组化法检测Bax和Bcl-2蛋白的表达。结果:联合治疗组的肿瘤生长速度明显慢于PBS组(P=0.003)和DTIC组(P=0.022);Ad·mda-7单用或与DTIC联合应用都可使肿瘤组织表达MDA-7蛋白;联合治疗组的凋亡指数明显高于其他各组(P<0.05);Ad·mda-7与DTIC都可以上调Bax的表达和下调Bcl-2表达,二者联合应用的作用更为显著(P<0.05)。结论:Ad·mda-7与DTTiC联合应用可以明显抑制人恶性黑素瘤细胞裸鼠移植瘤的生长,促进肿瘤组织凋亡。

Objective： To assess the effects of Ad·mda - 7 in combination with DTIC on human malignaut melanoma cell in nude mice. Methods： Human malignant melanoma cells were transplanted into nude mice. After the tumor - bearing nude mice were treated with PBS, Ad·mda - 7, DTIC or Ad·mda - 7 in combination with DTIC, the tumor volume was measured. The expression of MDA - 7 was detected by Western Blot. Apoptosis of cancer tissue was detected by TUNEL staining, the expression of Bax and Bcl - 2 by immunohisto - chemistry staining. Results： The tumor growth was slower in the group treated with Ad·mda - 7 and DTIC than in PBS group （ P = 0. 003 ） and DTIC group （ P = 0.022） ; Western blot showed there were the expressions of MDA - 7 protein in tumor cells measured both in Ad·mda- 7 group and in combination with DTIC group. Apoptosis index was significantly higher in combined treatment group than in any other group （ P 〈 0.05） ; Both Ad·mda - 7 and DTIC enhanced expression of Bax and decreased the expression of Bcl - 2. The effect was more significant in the group treated in combination （ P 〈 0.05）. Conclusion： These results suggest that Ad·mda - 7 in combination with DTIC can inhibit the growth and promote apoptosis of human malignant melanoma cells in nude mice, which may have potential clinical implications.