雷帕霉素抑制人前列腺癌细胞PC-3生长及转移的实验研究

Studies on inhibitory effect of rapamycin on growth and metastasis of PC3 cells

目的观察雷帕霉素（RPM）对人前列腺癌细胞PC-3生长、周期、凋亡及转移的影响，探讨RPM抑制前列腺癌细胞生长、转移的可能机制及临床应用前景。方法体外培养前列腺癌PC-3细胞，用不同浓度的RPM（10、25ng／m1）干预PC-3细胞。采用MTT法检测RPM对于PC-3细胞增殖的影响；流式细胞仪检测PC-3细胞周期及凋亡的变化；动物体内荷瘤实验检测对PC-3侵袭转移的影响。结果RPM能显著抑制PC-3细胞生长增殖，且呈时间和浓度依赖性，在25ng／36h时抑．ml36h制率达到（42．23±0．78）％，差异有统计学意义（P〈0．05）；流式细胞分析显示RPM能显著抑制细胞周期，使Go／G，期细胞增多（P〈0．05），在25ng／ml、36h时Go／G1期细胞达到（92．17±0．69）％，并促进肿瘤细胞的早期凋亡（P〈0．05），在25ng／ml、36h时凋亡率达到（28．75±1.31）％；动物体内荷瘤实验较对照组差别明显，对照组肿瘤重量与转移比率明显高于RPM组[（3．41±0．28）gVS（1．19±0．23）g，100％（7／7）vs 14．29％（1／7），P〈0．05]，肿瘤增长和转移被显著抑制。结论RPM明显抑制人前列腺癌细胞PC-3的生长及迁移，以RPM为基础的前列腺癌治疗方案可能在临床中具有良好的应用前景。

Objective To observe the effect of rapamycin on the proliferation and cell cycle of prostate cancer cell lines PC3, and to investigate the mechanism that it inhibits the growth and metastasis of prostate cancer cells. Methods PC3 cells were cultured in vitro, and treated with different concentrations （10, 25ng/ml） of cycle raparnycine. MTr was used to measure the change of proliferation of PC3 cells. Flow cytometry was used to measure the changes of cell cycle and apoptosis of PC3 cells. Nude mice were used to detect the effect of rapamycin on metastasis. Results The proliferation of PC3 cells was significant- ly inhibited by rapamycin, and a time- and concentration-dependent relationship was shown, the inhibited rate was（42.23±0.78）% after 36 h in the group of 25 ng/ml （ P 〈0.05）. Flow eytometry analysis showed rapamycin significantly inhibited the cell cycle, prompted the apoptosis, and increased the number of cells in G0/Gt phase at 36 h with a rate of cell staying at G0/G1 [ （92. 17±0. 69）% ] （ P 〈0. 05）. The weight of tumors in nude mice in the control group was significantly greater than that in RPM group[ （3.41± 0.28 ） g vs （ 1.19 ±0. 23 ） g ] （ P 〈 0.05 ）, and metastatic sites of the lung and liver in the control group were significantly more than the RPM group [ 100% （7/7） vs 14. 29% （1/7） ] （ P 〈0. 05）. Conclusions Rapamycin significantly inhibits the proliferation and metastasis of osteosarcoma. The rapamycin-based regimen is valuable for clinical application.