Inhibition of cell proliferation and mechanism research of an indazole derivative DY386 in prostate cancer / 中国药理学通报

ABSTRACT

Aim To investigate the anticancer activity of DY386 in a variety of cancer cells and the molecular mechanism of DY386 on cell cycle arrest in DU145 cells. Methods MTT assay was used to determine the inhibitory effect of DY386 on the growth of tumor cells including prostate tumor cell lines DU145, PC-3 ; glioblastoma cell line U87, non-small cell lung cancer cell lines H1975, HCC827, breast cancer cell line MCF-7, hepatoma cell line Hep3B and colon carcinoma cell line SW620. Colony formation assay and BrdU staining assay were performed to check the suppressive activity of DY386 to DU145 cell proliferation. Flow cytometry was conducted to evaluate the cell cycle distribution of DU145. Western blot was performed to detect the pro-tein level of cyclinBl, cyclinEi, CDK2, p27. Results DY386 inhibited cell growth in previous described tumor cell lines, especially in DU145 cells with half maximal inhibitory concentration (IC) value of 11.86 (imol • Flow cytometry analysis indicated that DY386 induced S phase arrest in DU145 cells. Furthermore, Western blot results revealed that DY386 decreased the expression of cyclinEi and cyclinBl and increased the expression of p27 in a dose-dependent manner. Conclusions DY386 reveals certain antitumor effect, and its mechanism may be related to inhibiting cell proliferation by blocking cell cycle.