The anti-proliferative effects of sPDZD2 on prostate and non-prostate cancer cells

Abstract

The PDZ domain containing protein 2 (PDZD2) is believed to be involved in the prostate cancer development and it can be cleaved by caspase-3 to produce a 37kDa secreted protein sPDZD2 in prostate cancer cell lines. Our laboratory has previously shown that sPDZD2 can inhibit the proliferation of DU145 prostate cancer cells and promote apoptosis in LNCaP prostate cancer cells.

By using a nude mice xenograft model, we investigated the effects of sPDZD2 under in vivo conditions. DU145 cells were subcutaneously injected into nude mice, and the mice were either intraperitoneally injected daily with low dose (0.084 mg) or high dose (8.4 mg) of recombinant sPDZD2. The volumes of the tumors were then measured weekly. There was a significant decrease in tumor volume in nude mice treated with high dose (8.4 mg) sPDZD2 as compared with the control group. Moreover, the biological effects of sPDZD2 on human non-prostate cancer cells were examined. Using cell count and MTS assays, it was found that 10 nM and 100 nM of sPDZD2 induced anti-proliferative effects on hepatocellular carcinoma Hep-G2 cells and hormone-sensitive breast adenocarcinoma MCF-7 cells, but not colon adenocarcinoma LoVo cells, renal carcinoma 786-O cells, hepatocellualr carcinoma Hep-3B cells and hormone-insensitive breast adenocarcinoma MDA-MB-468 cells.

The work was supported by Research Grants HKU7474/04M (to K-MY) and the HKU7580/05M (to SYWS).