ABSTRACT
Objective To investigate the androgen-like effects of Cordyceps sinensis (CS) and its impact on the radiosensitivity of VCaP prostate cancer cells.Methods The hormone levels and weight index of reproductive organs in mice were determined after gavage with CS.Clonogenic assay was performed to determine the impact of CS on the radiosensitivity of VCaP cells.The 3-(4,5-dimethylthiazol-2-yl)-5 (3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay,flow cytometry,and tumor xenografts in nude mice were performed to determine the effects of CS on the proliferation of VCaP cells (androgen receptor-positive) and PC-3 cells (androgen receptor-negative) in vitro and in vivo.Serum prostate-specific antigen (PSA) levels in nude mice were evaluated.Data were analyzed by one-way analysis of variance or ttest.Results The testosterone level and weight of prostate in mice were significantly higher in the CS group than in the control group ((8.28± 1.94) vs.(2.08± 1.24) ng/ml,P=0.023;(0.53±0.04) vs.(0.31 ± 0.04) mg/g,P =0.006).The radiosensitivity enhancement ratio (ratio of D0 values) was 0.80.The viability of VCaP cells was significantly higher in the CS group than in the control group (1.32 ± 0.07 vs.0.66 ±0.02,P=0.000),and colony forming efficiency was significantly enhanced in the CS group than in the control group (57.0％ ± 1.9％ vs.47.0％ ± 0.6％,P =0.005).VCaP tumor xenografts in nude mice were inclined to grow faster in the CS group than in the control group,and the serum PSA level in the CS group was significantly higher than that in the control group ((0.66 ± 0.04) vs.(0.26 ±0.06) ng/ml,P =0.000).However,CS had no effect on PC-3 cells at the working concentration.Conclusions CS has the androgen-like effects.It may also promote the proliferation and reduce the radiosensitivity of androgen receptor-positive VCaP cells.
ABSTRACT
PURPOSE: We determined the effect of tyrosine kinase inhibitor(TKI), ZM260603 on the growth of prostate cancer cell lines. MATERIALS AND METHODS: Using the synthetic TKI, ZM260603, cytotoxicity test and cell cycle analysis were performed on LNCaP, DU-145 and PC3 prostate cancer cell lines. The bcl-2 and bax protein expressions were observed in PC3 prostate cancer cell line by western blotting. The inhibitory effect of TKI was determined under the presence or absence of dehydrotestosterone, in androgen-dependent LNCaP prostate cancer cell line. RESULTS: The synthetic TKI, ZM260603 showed definite cytotoxicity on all prostate cancer cell lines studied regardless of androgen-dependency. The IC50 were 0.35+/-0.08microM, 0.12+/-0.06microM and 0.21+/-0.09microM for LnCaP, DU-145 and PC-3 cell lines, respectively. The G0/G1 phase arrests were observed commonly in all of these cell lines by flowcytometric analysis. Decrement in bcl-2 expression and increment of bax protein expression in the PC-3 cell line was observed by western blotting. The IC50 of hormone-dependent LNCaP prostate cancer cell line on TKI was increased about four folds by the addition of dihydrotestosterone. CONCLUSIONS: Our results suggest that the changes in the expression of bcl-2 and bax proteins are related with inhibitory process of the synthetic TKI, ZM260,603 on the growth of prostate cancer cell lines. Androgen seems to act as compromising or weakening the effects of TKI in androgen-dependent prostate cancer cell line, although the exact relationships between androgen-dependency and bcl-2 expression are unclear.