摘要
目的 从能量生成角度研究京尼平(Genipin)对激素非依赖性前列腺癌(AIPC)的抑制作用是否与线粒体解耦联蛋白2(UCP2)被阻断有关,并探讨其临床意义.方法 以低、中、高(40、80、120 μmol/L)剂量Genipin干预PC-3细胞培养基48 h,噻唑蓝(MTT)和流式细胞仪检测细胞增殖及凋亡,实时荧光定量聚合酶链反应(Real-time PCR)、Western blot检测UCP2表达,荧光探针检测细胞内Ca2含量,分光光度计检测线粒体膜电势(△ψm)、膜通透性转换孔(mPTP)变化及三磷酸腺苷(ATP)含量.结果 Genipin能显著抑制PC-3细胞增殖,其中对照组及低、中、高剂量组细胞凋亡率分别为(7.60±1.48)%、(9.38±1.01)%、(20.77±1.14)%、(23.48±1.99)%,Genipin可降低UCP2表达,此时细胞内Ca2含量明显增加,且mPTP开放程度增加及△ψm减小,ATP生成明显减少,其中对照组及低、中、高剂量组ATP含量分别为(0.120 ±0.015)、(0.110 ±0.013)、(0.080 ±0.007)、(0.050 ±0.008) mmol/L,以上改变均与Genipin浓度呈正相关,且各组间比较差异均有统计学意义(P<0.05).结论 Genipin能明显抑制AIPC细胞的增殖,该抑制作用可能与其阻断UCP2,导致线粒体功能异常,ATP生成减少有关.
Objective To investigate whether uncoupling protein 2 (UCP2) blocked was participated in genipin inhibiting proliferation of androgen independent prostate cancer cells from the perspective of energy,and to explore its clinical significance.Methods PC-3 cells were cultured in vitro,three concentrations of genipin solutions were added to the culture medium.The differences in proliferation,apoptosis,expressions of UCP2,levels of Ca2+,mitochondrion membrane potential (△ψm),membrane permeability transition pore (mPTP) and adenosine triphosphate (ATP) between before and after treated with various concentrations of genipin were measured by methyl thiazolyl tetrazolium (MTT) assay,flow cytometry assay,Real-time polymerase chain reaction (PCR) assay,Western blotting assay,spectrophotometer assay respectively.Results Genipin significantly suppressed the growth of PC-3 cells.After treatment with different concentration of genipin for 48 h,the apoptosis rate of PC-3 cells was (7.60 ± 1.48) %,(9.38 ±1.01) %,(20.77 ± 1.14) % and (23.48 ± 1.99) % respectively,expression of UCP2 was significantly reduced,contents of Ca2+ and mPTP open degree were significantly increased,level of △ψm and contents of ATP were significantly reduced simultaneously,the contents of ATP was (0.120 ± 0.015),(0.110 ± 0.013),(0.080 ± 0.007) and (0.050 ± 0.008) mmol/L respectively.The above changes with genipin as a dose-dependent manner,and the differences were statistically significant (P 〈 0.05).Conclusion Genipin significantly inhibited the growth of androgen independent prostate cancer cells,of which may occur through down-regulating the expression of UCP2,resulting in mitochondrial dysfunction and ATP production decreased.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2014年第12期2664-2666,共3页
Chinese Journal of Experimental Surgery
基金
贵阳市科技局资助项目(筑科合同[2011103]26号)
关键词
激素非依赖性前列腺癌
京尼平
解耦联蛋白2
抑制
Androgen independent prostate cancer cells
Genipin
Uncoupling protein 2
Inhibition