雷帕霉素和紫杉醇对激素非依赖性前列腺癌细胞株影响的体外实验研究

Effects of rapamycin and paclitaxel on different human prostate cancer cells and xenografts

目的通过前列腺癌细胞株的体外实验对照研究初步探讨雷帕霉素、紫杉醇及两者联合应用对激素非依赖性前列腺癌细胞株的影响。方法分别采用噻唑蓝（MTT）比色法和流式细胞技术观察雷帕霉素、紫杉醇、雷帕霉素＋紫杉醇对不同前列腺癌细胞株（LNCaP—CA、LNCaP—CA-2、PC-3）细胞增生及细胞凋亡的影响。结果对于LNCaP—CA细胞株，同对照组相比，当雷帕霉素浓度为0．01μmol／L时，其抑制肿瘤细胞的作用开始出现显著性差异；而对于LNCaP—CA-2、PC-3细胞株，雷帕霉素浓度为0．001μmol／L时，其抑制肿瘤细胞的作用同对照组相比具有显著性差异。当紫杉醇浓度为0．2ng／mL时，同对照组相比，紫杉醇表现对3种前列腺癌细胞株有显著的抑制作用（P〈0．05），随着紫杉醇浓度的提高，其抑制肿瘤细胞的作用也越强。10nmol／L的雷帕霉素、1ng／mL的紫杉醇对前列腺癌细胞株的抑制作用同对照组相比已经有了显著性差异（P〈0．05），而5nmol／L的雷帕霉素＋0．5ng／mL的紫杉醇组对所有3种前列腺癌细胞株的抑制作用均显著高于10nmol／L的雷帕霉素组和1ng／mL的紫杉醇组。结论雷帕霉素和紫杉醇对3种前列腺癌细胞株（LNCaP—CA、LNCaP-C4-2、PC-3）均有一定抑制作用，且表现为剂量依赖关系。小剂量的雷帕霉素和紫杉醇联合应用可以起到更好的抑制肿瘤细胞的作用。

Objective To observe the anti-proliferation effects of rapamycin and paclitaxel of different human prostate cancer cells in vitro. Methods The methods of MTT and flow cytometry were respectively applied to observe the effect of rapamycin, paclitaxel and rapamycin ＋ paelitaxel on proliferation and apoptosis of different prostate cancer cell lines （ LNCaP-CA, LNCaP-C4-2, PC-3）. Results When the concentration of rapamycin was 0.01 μmol/L, the impressive effect showed a remarkable difference in contrast to the con- trol. While in group LNCaP-C4-2 and PC-3, the goal concentration of rapamycin was 0.001 μmol/L. When the concentration of paclitaxel was 0. ：2 ng/mL, the impressive effect showed a remarkable difference in contrast to the control. In group rapamycin （ 10 nmoL/L） and in group paclitaxel （ 1 ng/mL） there were significant differences in growth inhibition, compared with control. While in group rapanlyein（5 nmol/L） ＋ paclitaxel（0.5ng/mL） there was significant difference in growth inhibition, compared with rapamycin （10 nmol/ L） and paclitaxel （1 ng/mL） respectively. After cultured with rapamycin or paclitaxel alone, more tumor ceils induced apoptosis than control. While after cultured with rapamycin and paclitaxel simultaneously, more tumor cells induced apoptosis than with rapamycin or paclitaxel alone. Conclusions Both rapamycin and paclitaxel had a good impressive effect on the three prostate cell lines （LNCaP-C4, LNCaP-CA-2, PC- 3） with dose-dependent manner. After cultured with rapamycin and paclitaxel simultaneously, more tumor cells were induced apoptosis than with rapamycin or paclitaxel alone.