^(32)P胶体致人胰腺癌Pc-3移植瘤细胞凋亡及其相关基因表达的研究

Study on the apoptosis and expression of correlated genes induced by ^(32)P chromic phosphate colloid on grafted pancreatic carcinoma Pc-3 in nude mice

目的 观察低剂量32 P胶体瘤体内注射诱导裸鼠人胰腺癌Pc 3移植瘤细胞凋亡的生物学效应、相关基因的表达及其可能的作用机理。方法 建立BALB c裸鼠人胰腺癌Pc 3移植瘤动物模型 ,分别向 3 0只荷瘤鼠瘤块中心注射不同剂量 (0 3 7、0 74、1 48、2 96和 5 92MBq)的3 2 P胶体溶液 ,对照组注射等体积冷胶体。于注射后 2 4h取出瘤块 ;通过流式细胞仪、透射电镜及免疫组织化学检测等方法 ,研究肿瘤组织的细胞凋亡率、细胞坏死率、细胞超微结构改变及Apo2 7、Caspase 3、bcl 2、bax相关基因的表达。结果 0 74、1 48和 2 96MBq组瘤体内注射后电镜下可见典型的细胞凋亡表现 ,5 92MBq组细胞则以大量坏死为主。辐射诱导凋亡过程中 ,bcl 2 bax比值下调 ,Apo2 7、Caspase 3蛋白表达均明显增加。结论 32 P胶体瘤体注射可诱导荷瘤裸鼠人胰腺癌Pc 3肿瘤细胞凋亡 ;Apo2 7、Caspase 3、bcl

Objective To observe the biologic effects of apoptotic changes of tumor cells in nude mice bearing the solid tumor of pancreatic carcinoma Pc-3 after interstitial i rradi tion with low-dose 32 P chromic phosphate colloid, and to investig ate the potential mechanisms of the effects. Methods Thirty BALB/c nude mice bearing Pc-3 human pancreatic carcinoma tumor xenograft were used in the study. After intratumoral injection of 32 P colloid at the dos es of 0.37, 0.74, 1.48, 2.96 and 5.92 MBq for the study groups, and injection of nonradioactive colloid for the control group, the mice were sacrificed at 24 h after intratumoral injection and the grafted tumors were picked out. The flow cy tometry, transmission electron microscopy and immunohistochemistry were used to investigate the cell apoptosis rate, cell necrosis rate, cell ultrastructural ch anges and related gene expression of Apo2.7, Caspase-3, bcl-2 and bax. R esults The typical apoptosis was observed in 0.74, 1.48 and 2.96 MBq grou ps by transmission electron microscopy. The necrosis was most obvious in the 5.92 MBq group. The ratio of bcl-2 to bax protein decreased duri ng the apoptosis induced by radiation, both the expression of Apo2.7 and Caspase -3 increased apparently. Conclusion The interstitial injection of radionuclide 32 P to the nude mice bearing human pancreatic carcino ma Pc-3 can induce the apoptosis of Pc-3 cells, both the protein Apo2.7 and C aspase-3, and the related genes of bcl-2 and bax were involved in the apoptosi s induced by radiation.