吉西他滨与奥曲肽联合应用对前列腺癌细胞PC-3的抑制作用

目的 研究吉西他滨与奥曲肽联合用药对去势抵抗性前列腺癌细胞PC-3增殖的抑制作用及对凋亡的影响.方法 体外培养人前列腺癌细胞株PC-3,应用MTT细胞实验研究空白组、对照组、不同浓度的奥曲肽组(0.5μg/mL、1μg/mL、2μg/mL、4μg/mL、8μg/mL)与吉西他滨组(1μg/mL)单独使用以及联合使用不同时间段对PC-3细胞增殖抑制的影响;应用流式细胞仪检测对照组、奥曲肽组(8μg/mL)与吉西他滨组(1μg/mL)单独使用及联合使用对PC-3细胞凋亡的影响;并用Western-blot实验研究对照组、奥曲肽组(8μg/mL)与吉西他滨(1μg/mL)单独使用及联合使用对凋亡指标Bax、Bcl-2、Caspase3、Caspase9表达的影响.结果 MTT细胞实验显示,联合用药组作用72 h后,抑制率可达62%,显著高于对照组、奥曲肽组和吉西他滨组,差异均有显著统计学意义(P<0.05);AnnexinV-FITC细胞凋亡实验结果表明,联合用药组凋亡率25%,显著高于对照组、奥曲肽组和吉西他滨组,差异均有显著统计学意义(P<0.05);Western-blot结果显示,联合用药组Bcl-2表达低于对照组、奥曲肽组和吉西他滨组,而其Bax,Caspase3、Caspase9蛋白表达量显著高于对照组、奥曲肽组和吉西他滨组,差异均有统计学意义(P<0.05).结论 吉西他滨和奥曲肽可以协同作用,增强对去势抵抗性前列腺癌细胞系PC-3的增殖抑制和促凋亡作用,提示临床上两者联合应用于去势抵抗性前列腺癌治疗的可行性.

Synergistic inhibition effects of gemcitabine and octreotide on prostate cancer cell line PC-3

Objective To study the inhibitory effects of gemcitabine cooperated with octreotide on castration resistant prostate cancer cells PC-3 proliferation and the influence on apoptosis. Methods Human prostate cancer cell line PC-3 was cultured in vitro in order to investigate the effects of octreotide (0.5 μg/mL, 1 μg/mL, 2 μg/mL, 4 μg/mL, 8 μg/mL) and gemcitabine (1μg/mL) alone or combination on proliferation inhibition and apoptosis-inducing ability in different periods of time. Flow cytometry was applied to study the effects of octreotide (8 μg/mL) and gemcitabine (1μg/mL) alone or combination on PC-3 cell apoptosis. And Western-blot technique was utilized to evaluate the influ-ence of octreotide (8 μg/mL) and gemcitabine (1μg/mL) alone or combination on expression of apoptosis indexes Bax, Bcl-2, Caspase3 and Caspase9. Results MTT cell test results showed that after 72 hours, the inhibition ratio was 62%in combined treatment group, significantly higher than that in the single drug group and control group, showing the dif-ferences were statistically significant (P<0.05). AnnexinV-FITC cell apoptosis experiment results showed that the apop-tosis rate in combined treatment group (25%) was significantly higher than that of the single drug group and control group, showing the differences were statistically significant (P<0.05). Western-blot experiment results showed that the Bcl-2 in the combined treatment group was lower than that in other groups, and the expression of Bax, Caspase3 and Caspase9 protein were significantly higher than that in other groups, showing the differences were statistically signifi-cant (P<0.05). Conclusion The synergistic effect of octreotide and gemcitabine enhanced the proliferation inhibition and apoptosis promotion in human castration resistant prostate cancer cell line PC-3, suggesting that the clinical combi-nation should be feasible for the treatment of castration resistant prostate cancer.