Lysophosphatidic Acid Modifies the Response of PC3 Prostate Cancer Cells to Chemotherapeutics

Abstract

OBJECTIVE: Prostate cancer is the most frequently diagnosed cancer among men. Docetaxel, estramustine, and mitoxantrone are commonly used chemotherapy agents for the treatment of prostate cancer. However, lysophosphatidic acid (LPA), a biologically active glycerophospholipid derivative, induces proliferation and inhibits apoptosis in prostate cancer cells. The aim of this study was to investigate the effects of LPA against cell toxicity of docetaxel, estramustine and mitoxantrone. MATERIALS AND METHODS: Prostate carcinoma PC3 cells were separately treated with docetaxel, estramustine and mitoxantrone in combinations with LPA. BrdU incorporation assay was used to assess the cell proliferation. Besides, colony forming ability of cells were measured by staining with crystal violet. The ratio of apoptotic cells was also detected by flow cytometry. RESULTS: All the chemotherapeutic drugs decreased the proliferation and colony formation of PC3 cells whereas these parameters were found to be significantly increased in the cells treated with LPA alone. Treatment of drugs together with LPA increased cell proliferation and colony formation compared to the treatment of with drugs alone. Also, LPA was seen to modify the apoptotic effects of docetaxel, estramustine and mitoxantrone. CONCLUSIONS: Our results showed that LPA contributed to cell survival and proliferation in PC3 prostate cancer cells. LPA created a resistance against cell death induced by docetaxel, estramustine and mitoxantrone. Our study supports the idea that LPA or its signaling pathways may be a promising target for the treatment of prostate cancer and prevention of resistance to chemotherapy.

Keywords

• apoptosis
• cell proliferation
• docetaxel
• estramustine
• lysophosphatidic acid
• mitoxantrone
• prostate cancer