hTERT启动子驱动的TRAIL联合放化疗对HeLa裸鼠移植瘤生长抑制的作用

Inhibitory effect of hTERT promoter regulated tumor targeting TRALL combined with chemo-radiotherapy on cervical cancer in vivo

目的：探讨hTERT启动子驱动的TRAIL联合放化疗对宫颈癌HeLa裸鼠皮下移植瘤生长抑制的作用.方法：将含有hTERT启动子的TRAIL基因载体转染宫颈癌细胞HeLa,检测稳定转染细胞中GFP/TRAIL的表达;实验裸鼠分为基因组,化疗组,放疗组,综合组（基因＋放化疗）,对照组,每组5只,未转染HeLa组为对照组,不作任何处理;将稳定转染基因载体及未转染的HeLa细胞种植于裸鼠背部皮下,联合放化疗,来观察移植瘤成瘤情况,移植瘤的体积、质量以及质量抑制率的变化.结果：转染hTERT-TRAIL细胞中GFP/TRAIL（绿色荧光蛋白）表达率高于对照组,有统计学意义（P〈0.01）;各组裸鼠在接种细胞第5~7日全部长出肿瘤小结节,结节出现的时间差异无统计学意义（P〉0.05）;转染hTERT-TRAIL细胞与对照组HeLa细胞裸鼠的移植瘤质量相比差异有统计学意义（P〈0.05）;hTERT-TRAIL细胞在裸鼠体内所形成的移植瘤生长较慢,4wk后肿瘤质量抑制率为43.08%,联合放化疗后肿瘤质量抑制率为61.63%,有统计学意义（P〈0.01）.结论：hTERT启动子驱动的TRAIL对人宫颈癌裸鼠移植瘤有明显的抑制作用,联合放化疗能抑制裸鼠移植瘤的生长.基因治疗联合放化疗等多途径综合治疗为以后的肿瘤研究和临床治疗提供思路.

AIM： To study the inhibitory effect of hTERT promoter regulated TRALL combined with chemoradiotherapy on the growth of transplantation tumor of HeLa cells in nude mice. METHODS： The TRAIL gene activated by the bTERT promoter was transfected into HeLa cells; The GFP protein expression of TRAIL was examined by immunobistocbemical staining;The rats were divided into TRAIL gene transfection group, chemotherapy group, radiotherapy group, combined treatment group （ genetransfection ＋ cbemo-radiotherapy） , and control group, with 5 rats in each group. The TRAIL gene transfected cells and the blank HeLa cells were seeded in mice subcutaneously. The combinded effects of TRAIL with cbemo-radiotberapy on the nodulation of the cervical cancer HeLa lines were detected. The changes of tumor weight, sizes, and the tumor growth inhibition rate were determined. RESULTS ： GFP/TRAIL expression rate was significantly higher in bTERT_TRAIL transfected cells than in control cells（P 〈 0.01 ）. Nodulation of HeLa cells was observed on day 5-7 in all group, with no difference in nodulation generation time （P 〉 0.05 ）. The transplanted tumor weight was significantly different between transfected bTERT-TRAIL group and control group （P 〈 0.05 ）. The transplanted tumors in bTERT-TRAIL grew slowly compared to control group. The tumor growth inhibition rate was 43.08% in bTERT-TRAIL group and 61.63% in the gene transfection plus radio-chemotherapy group at week 4 （P 〈0. 01 ）. CONCLUSION ： hTERT-TRAIL exerts obvious inhibitory effects on the growth of HeLa cells transplanted tumor in nude mice. The gene transfection plus radio-chemotherapy may enlighten the future preclinical study and clinical therapy for tumors.