^125Ⅰ粒子对前列腺癌PC-3移植瘤bcl-2、bax基因表达和细胞凋亡的影响

The bcl-2, bax gene expression and apoptosis of continuous low-dose-rate irradiation on PC-3 transplanting tumor

目的探讨^125Ⅰ粒子持续低剂量率照射对前列腺癌PC-3移植瘤bcl-2、bax基因表达和细胞凋亡的影响。方法利用2枚37MBq^125Ⅰ粒子模型对前列腺癌PC-3移植瘤裸鼠进行48，96和192h照射，用免疫组织化学方法分析bcl-2和bax基因表达情况。用原位末端标记（TUNEL）法检测凋亡率。凋亡率和bax／bcl-2比值之间的相关性采用线性相关分析。统计学处理采用SPSS 11．0软件。结果^125Ⅰ粒子持续低剂量率照射48h后bcl-2表达下降到4．00±2．00，与对照组比较差异无统计学意义（t=2．500，P=0．067）；96和192h后bcl-2表达分别下降到2．67±1．16和3．00±1．00，与对照组比较差异有统计学意义（t=4．950，3．464；P=0．008，0．026）。bax表达分别上升到11．33±2．89，8．67±1．16和8．67±1．16，与对照组比较差异有统计学意义（t=3．334，4．025，5．292；P值分别为0．029，0．016和0．006）。^125Ⅰ粒子持续低剂量率照射48h组PC-3细胞凋亡率为22．3％，与对照组比较差异无统计学意义（P=0．404）；照射96和192h组凋亡率增加到21．7％和30．7％，与对照组比较差异有统计学意义（P=0．016，0．036）。各照射组之间凋亡率差异无统计学意义（P〉0．05）。^125Ⅰ粒子持续低剂量率照射PC-3细胞凋亡率和bax／bcl-2比值呈正相关（r=0．784，P=0．012）。结论”I粒子持续低剂量率照射可使PC-3细胞bcl-2表达下降，bax表达上升，诱导凋亡增加，而凋亡率与bax／bcl-2比值呈正相关。^125Ⅰ粒子对肿瘤细胞的抑制可能通过bcl-2、bax途径诱导细胞凋亡而发挥作用。

Objective The aim of this study was to investigate bcl-2,bax expression and apoptosis of continuous low-dose-rate irradiation on prostate cancer （ PC ） -3 transplanting tumor. Methods The expression of bcl-2 and bax associated with apoptosis between experiment and control groups were analyzed using immunohistochemistry at 48, 96 and 192 h after two ^125Ⅰ seed sources implanting model. The correlation between apoptosis and the ratio of bax/bcl-2 was analyzed using Bi-variable linear correlation. SPSS 11.0 was used to analyse the data. Results The bcl-2 expression in experiment group began to down-regulated significantly after ^125Ⅰ seed irradiation for 48 h as compared with control（ t = 2. 500,P = 0. 067 ） , though it was not reached to statistical significance. At 96 and 192 h after irradiation, significantly low expression of bcl- 2 were noted （ t = 4. 950, 3. 464 ; P = 0. 008 and 0. 026）. In contrast, significantly over expression of bax was noted at 48, 96 and 192 h after ^125Ⅰ irradiation （t=3. 334,4. 025,5. 292;P =0. 029, 0. 016 and 0. 006）. The apoptotic index （AI） for PC-3 at 48, 96 and 192 h after ^125Ⅰ irradiation were 22. 3%, 21.7% and 30.7%, which was significantly higher than controls when at 96 and 192 h after ^125Ⅰ irradiation （ P = 0. 016 and 0.036）. Moreover, positive correlation was noted between AI and bax/bcl-2 ratio （ r =0. 784, P = 0. 012）. Conclusion Low-dose-rate irradiation could down-regulate the expression of bcl-2, up-regulate the expression of bax and induced PC-3 cells apoptosis.