尹卫华+夏红梅+罗小瑾+徐荣+胡小雄

[摘要]目的 观察沙利度胺对前列腺癌PC3细胞增殖和凋亡的作用及其IL-6和Cx43表达的影响。方法 将递增浓度6.25、12.50、25.00、50.00、100.00 μg/ml沙利度胺加入处于对数生长期的前列腺癌PC3细胞培养。采用MTT法检测不同浓度沙利度胺对PC3细胞的增殖抑制影响，Annexin PI双染色法检测PC3细胞凋亡情况，ELISA法检测PC3细胞中IL-6和Cx43的表达。结果 25.00、50.00、100.00 μg/ml沙利度胺能明显抑制PC3细胞体外增殖，随着时间延长、浓度增加，增殖抑制率相应升高；IL-6表达随沙利度胺浓度增加而下降（r=-0.924，P=0.009），Cx43表达与沙利度胺浓度成正相关（r=0.915，P=0.010）。结论 沙利度胺可通过抑制人前列腺癌PC3细胞IL-6表达、上调Cx43水平，可能恢复细胞缝隙连接通讯功能来抑制肿瘤细胞增殖、诱导其调亡，从而达到抗肿瘤效果。

[关键词]沙利度胺；前列腺癌；白介素-6；连接蛋白43

[中图分类号] R737.25 [文献标识码] A [文章编号] 1674-4721（2017）02（b）-0008-04

[Abstract]Objective To observe the effects of Thalidomide on the proliferation and apoptosis of prostate cancer PC3 cells，as well as on the expression of the protein Cx43 and IL-6 in this cells.Methods Thalidomide with different concentrations （6.25，12.50，25.00，50.00，100.00 μg/ml） was added to PC3 cells at the logarithmic growth phase.MTT was used to detect the inhibitory effect of different concentration of Thalidomide on proliferation of PC3 cells，the apoptosis rate of PC3 cells was studied by Annexin V fluorescein isothiocyanate （Annexin PI） double staining with flow cytometry.Enzyme-linked Immunosorbnent assay method was used to detect the expression of IL-6 and Cx43 in PC3 cells.Results Below 25.00，50.00，100.00 μg/ml，Talidomide significantly inhibited the proliferation of PC3 cells in vitro，and the inhibition rate increased with the increase of time and concentration，the expression of IL-6 decreased with the increasing of concentration（r=-0.924，P=0.009），the expression of Cx43 had positive correlation with the concentration of thalidomide（r=0.915，P=0.010）.Conclusion Thalidomide can inhibit the expression of IL-6 in PC3 cells，increase the expression levels of Cx43，restore the functional refreshment of gap junction intercellular communication function in prostate cancer PC3 cells for in inhibiting the proliferation of PC3 cells and inducing its apoptosis，in order to inhibit the growth of tumor.

[Key words]Thalidomide；Prostate cancer；Interleulin-6；Connexin43

前列腺癌是目前男性最常見的泌尿系统恶性肿瘤之一，在西方国家，其死亡率位居恶性肿瘤的第2位[1-2]。近年来，我国前列腺癌发病率明显呈上升趋势[3-4]。早期前列腺癌采用去势治疗取得了一定的效果，18～24个月发展为激素非依赖性前列腺癌。目前激素非依赖性前列腺癌缺乏有效的治疗手段，是前列腺癌患者死亡的主要原因。虽然以紫杉醇类为基础的化疗药如多西他赛、卡巴他赛以及新药阿比特龙，Sipuleucel-T疫苗可改善激素非依赖性前列腺癌患者短期生存，但仍然逃脱不了耐药、免疫耐受的问题[5-6]。相关研究显示，前列腺癌进展可能与白介素-6（interleulin-6，IL-6）、连接蛋白43（Connexin43，Cx43）有关[7-11]。IL-6是具有强烈激发雄激素受体，上调肿瘤细胞VEGF的表达，是前列腺癌进展因素之一[7-8]。……