Inhibitory effect of griseofulvin on human prostate cancer PC-3 cells and Balb/c nude mice tumor xenograft / 中华泌尿外科杂志

ABSTRACT

Objective To study the anti-tumor effects of griseofulvin on human prostate cancer PC-3 cells both in vitro and in vivo. Methods PC-3 cells were treated with griseofulvin at various concentrations for48 h,cell survival rate was then measured by MTT assay.The changes of morphology were observed by fluorescence microscope; Annexin V-FITC apoptosis detection kit was used to detect apoptosis of the cells ; The enzyme activity changes of caspase-3,8,9 were detected by spectrophotometry.For in vivo study,we first established the PC-3 tumor model by grafting PC-3 cells in athymic nude mice,and then injected griseofulvin into the tumors.12 days after injection,the mice were sacrificed,the tumors were removed,weighed and the ratios of tumor-suppression were then calculated.We had detected the expressions of Bcl-2,Bax,p53 and Survivin with immumohistochemistry as well. Results MTT results showed that griseofulvin could significantly inhibit the proliferation of PC-3 cells in vitro in a dose-dependent manner,and the IC50 of griseofulvin was 18.17 ±2.10 μg/ml.Typical morphological changes of PC-3 cells were observed by microscope.The rates of apoptosis of griseofulvin treated PC-3 cells greatly increased compared with that of the control cells (31.37 ± 2.93％ vs 2.89 ± 0.67％,P ＜ 0.01 ).The caspase-3,caspase-8 and caspase-9 activities in griseofulvin treated PC-3 cells were significantly higher than those in control cells (0.562 ±0.050 vs0.113±0.014,0.337±0.053 vs 0.120±0.017,0.293±0.038 vs0.109±0.018,P＜0.01).On the 23th day after tumor vaccination,the tumor volume was 961.17 ± 78.12 mm3 in griseofulvin treated group and was 433.6 ± 12.8 mm3 in control group (P ＜ 0.01 ).The tumor weight was 742.50 ± 78.63 mg in griseofulvin treated group and was 1387.33 ± 71.47 mg3 in control group ( P ＜ 0.01 ).Bcl-2,Bax,p53 and Survivin protein expressions were 16.10 ± 3.45％,39.50 ± 6.88％,48.20 ± 8.04％,16.50 ± 2.22％ in griseofulvin treated group,respectively; 41.30 ± 3.95％,13.70 ± 2.98％,17.60 ± 3.21％,52.11 ± 6.28％ in control group,respectively.And there were significant differences in both groups (P ＜ 0.01 ).The in vivo data showed that griseofulvin suppressed the tumor growth conspicuously through down-regulating the expression of Bcl-2,Survivin,and up-regulating the expression of Bax,p53. Conclusions Griseofulvin can inhibit the growth of PC-3 and induce apoptosis of PC-3 cells.Griseofulvin inhibits the in vivo tumorigenicity of PC-3 cells.