^153Sm标记环九肽对人前列腺癌PC-3细胞的直接抑制作用

Direct inhibitory effects of ^153 Sm-DTPA-c （CGRRAGGSC） on human prostate cancer PC-3 cells

目的探讨^153Sm标记环九肽对人前列腺癌PC-3细胞生长的直接抑制作用。方法用间接法合成^153Sm-DTPA-半胱氨酰．甘氨酰-精氨酰-精氨酰-丙氨酰-甘氨酰-甘氨酰-丝氨酰一半胱氨酸[c（CGRRAGGSC）]。细胞生长抑制实验分为4组：对照（A）组100μlPBS，B组c（CGRRAGGSC）100μl（1．5mgCL），C组153SmCl3 370kBq（100μl），D组153Sm-DTPA-c（CGRRAGGSC）370kBq（100-）。采用四甲基偶氮唑蓝（Mrl3r）法检测不同组对人前列腺癌PC-3细胞24，48，72h的生长抑制作用；用流式细胞仪分析48h细胞凋亡及细胞周期变化；Western blot检测药物处理前及处理后48hPC-3细胞中自细胞介素11（IL11）及IL11受体（IL11R）表达。抑制率组间差异采用单因素方差分析，IL11R表达情况比较用配对t检验。结果153Sm—DTPA-c（CGRRAGGSC）标记率〉85％，放化纯〉95．8％，比活度为1．32×10^5MBq／μmol。A、B组未见细胞抑制，C、D组对细胞的抑制杀伤呈时间效应；各组药物作用48h后，通过亚G，峰检测的PC-3细胞凋亡率分别为（0．98±0．18）％，（0．35±0．10）％，（4．05±0．28）％，（13．38±0．89）％，差异有统计学意义（F=953．60，P〈0．05）。Western blot检测，B—D组IL11未见变化，IL11R表达D组比B、C组降低，干预后吸光度（A）值分别为0．339±0.014，0．338±0．019，0．226±0．015，与干预前比，B，C组差异均无统计学意义（t=0．405，1．163，P〉0．05），D组差异有统计学意义（t=135．989，P〈0．05）。结论153Sm-DTPA—c（CGRRAGGSC）能够直接抑制PC-3细胞的生长，并促进IL11R表达下调。

Objective To investigate the direct inhibitory effects of 153Sm- IYI＇PA-c （Cys-Gly-Arg-ArgAla-Gly-Gly-Ser-Cys） NH2 （ 153 Sm-DTPA-c （CGRRAGGSC） ） on human prostate cancer PC-3 cells. Methods 153Sm-DTPA-c（CGRRAGGSC） was synthesized by the reaction of 153SmCl3 with DTPA-c（CGRRAGGSC） using indirect synthesis method. PC-3 cells in vitro culture were divided into four study groups, groug A （the control, with PBS only）, group B with 1.5 mg/L c（CGRRAGGSC）, group C with 370 kBq 153SMC13 and group D with 370 kBq lS3Sm-DTPA-c（CGRRAGGSC）. PC-3 cell growth was assayed by 3-（4, 5-dimethylthiazol- 2-yl ） -2, 5-diphenyltetrazolium bromide （MTF） method. Cell cycle and apoptosis were analyzed by flow cytometry. The expression changes of interleukin 11 （IL11 ） and IL11 receptor （IL11R） in PC-3 cells were exmined by Western Blot. One way analysis of variance （ANOVA） and paired-t test were applied for statistic analysis. Results The labeling yield of 153Sm-DTPA-c （CGRRAGGSC） was 85% and the radiochemical purity was 95.8%. The specific activity of 153Sm-DTPA-c（CGRRAGGSC） was 1.32× 10^5 MBq/μmol. Significant inhibitory effects on the growth of PC-3 cells were found in both group C and D, with a time-dependent manner. However, no obvious inhibition was found either in group A or in group B. After 48 h, significant differences of sub-G1 peak area were found among groups, （0. 98 ± 0. 18）%, （0. 35 ±0. 10）% , （4.05 ±0.28）% and （13.38 ＋0. 89）% for group A, B, C and D, respectively. Furthermore,expression of IL11R in group D was significantly lower than that in group B and C with absorbance values 0. 339 ±0.014, 0. 338 ＋0.019, 0.226 ±0. 015 for group B, C and D, respectively. Absorbance values in groups B and C were not significantly different after treatment, compared with those before treatment; however, there was difference between absorbance values after and before treatment in group D （ t = 0. 405, 1. 163,135.989,P〉0.05 〉0.05, 〈0.05）. Conclusion 153Sm-DTPA-c（CGRRAGGSC） can directly inhibit the cell growth and expression of human prostate cancer cells PC-3.