临床有效剂量的洛伐他汀对前列腺癌PC3细胞的影响

Effects of clinically effective dose of lovastatin on prostate cancer PC3 cells

目的:研究临床有效剂量的洛伐他汀对前列腺癌PC3细胞的影响。方法:将PC3细胞分为空白对照组、二甲基亚砜(dimethyl sulfoxide,DMSO)对照组、洛伐他汀处理组、洛伐他汀与甲羟戊酸(mevalonic acid)同时处理组,处理时间点分别为24、48和72h。运用MTT方法检测细胞活力,[3H]掺入法和细胞计数法检测细胞增殖改变,Western blot检测凋亡关键分子casepase3、casepase7、多聚ADP-核糖聚合酶[poly(ADP-ribose)polymerase,PARP]裂解蛋白(cleaved PARP,cPARP)等。结果:临床有效剂量2μmol/L洛伐他汀作用PC3细胞48h后细胞增殖率比DMSO对照组降低了39.29%[(63.69%±3.69%)vs(102.98%±6.84%),P=0.000],72h后降低了44.24%[(52.79%±9.88%)vs(97.03%±0.87%),P=0.048];2μmol/L洛伐他汀作用PC3细胞72h后,数量显著减少[(4.86×105±0.10×105)vs(9.66×105±0.10×105),P=0.000];PC3细胞活力在2μmol/L洛伐他汀作用48和72h后分别降低了50.12%[(56.52%±6.40%)vs(106.64%±5.27%),P=0.000]和60.05%[(41.99%±11.64%)vs(102.94%±8.49%),P=0.000],此外,2μmol/L洛伐他汀还诱导凋亡关键分子caspase7活化及其受体PARP蛋白裂解。结论:临床有效剂量的洛伐他汀可抑制前列腺癌细胞PC3的增殖并诱导细胞凋亡。

Objective：To investigate the effects of clinically achievable dose of lovastatin on prostate cancer PC3 cells.Methods：PC3 prostate cancer cells were treated with dimethyl sulfoxide（DMSO）,or lovastain only,or lovastatin with mevalonic acid for 24,48 and 72 hours respectively.MTT assay was used to detect the cell viability.By means of [3H] thymidine incorporation tests,the effects of lovastatin on cell proliferation were analyzed.Western blot was used to detect activated casepase3,caspase7,and cleaved PARP（cPARP）,the important molecules on the apoptosis pathway.Results：Cell proliferation of PC3 was significantly inhibited by 39.29%[（63.69%±3.69%） vs（102.98%±6.84%）,P=0.000] after 48 h treatment with lovastatin at its clinically achievable dose of 2 μmol/L.After 72 hours the cell proliferation was inhibited by 44.24% [（52.79%±9.88%） vs（97.03%±0.87%）,P=0.048].The cell number was also markedly decreased（4.86×10^5 ± 0.10×10^5） vs（9.66×105±0.10×10^5）,P=0.000] after 72 h treatment at this low concentration of 2 μmol/L.The viability of PC3 cells was significantly decreased 50.12%（56.52%±6.40%） vs（106.64%±5.27%）,P=0.000] and 60.05%（41.99%±11.64%） vs（102.94%±8.49%）,P=0.000] after 48 h and 72 h treatment,respectively.In addition,2 μmol/L lovastatin induced activation of casepase7 and led the death substrate PARP to cleavage.Conclusion：Clinically achievable dose of lovastatin inhibits prostate cancer PC3 cell proliferation and induces PC3 cell apoptosis.