Effect of Synthetic Tyrosine Kinase Inhibitor(ZM260603) on the Growth of Prostate Cancer Cell Lines: Differences According to Androgen Dependency and Bcl-2 Expression

Hong, Sung Joon; Chung, Hyun Jik; Lee, Dong Hyun; Cho, Eun Song

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.