Role And Action Mechanism Of LPA In Proliferation And Migration Of Ovarian Cancer Cells

Background:Lysophosphatidic acid (LPA) is a bioactive phospholipid molecule, which is possible to regulate a series of physiological and pharmacological process through it’s six receptors (LPA 1-6) on the cell surface, play a role in cell proliferation, migration, adhesion, apoptosis, differentiation and secretion in many cell types. And closely related to the pathological process of pulmonary fibrosis, wound healing, and tumor development. In addition, LPA has been demonstrated to be an early biomarker for ovarian cancer, and reported to be accumulated with a high concentration in patients’ascites, which is an interesting topics, but its function related to the development of ovarian cancer and its mechanism is still unclear. In this study we found that LPA stimulated the human ovarian cancer cells proliferation, migration and futher clarified LPA receptor subtypes involved in the action. Furthermore, the signaling pathways mediated by LPA/LPARs were studied. Our results indicated that LPA receptors may be a potential target to establish therapeutic strategies for ovarian cancer. The study is important to understanding the role of physiological active lipid and the relationship between its function and tumor development.Methods and Results:CCK-8 assay was use to determine cell proliferation. Cell migratory activity was measured by the Micro chemotaxis chamber method, using Real Time PCR technology to detect human ovarian cancer (A2780/HO8910) LPA receptor expression. Then, the LPA1/LPA3 receptors were preferentially expressed. Pharmacological methods to verify the LPA1/LPA3 receptors involved in cell proliferation and migration. RNA interference technology is further to verify the involvement of the major LPA3 receptors. Types of G-coupled protein is determined by pre-treated with inhibiters specific to G-coupled proteins and Gai/o was verified. Protein expressions involved in the signaling pathways in responsible to LPA. MAP kinase inhibitor identified MAPK pathway is involved in the type of p38 and ERK, Transcription factors involved as NF-kB and the anti-apoptotic Bcl-2 in the process. At the same time measured MMP get involved in cell migration mechanisms.Conclusion:1. LPA promotes the cell migration by LPA3/Gai/o-MAPK-p38/ ERK-NF-kB-MMP.2. LPA/LPAR 3 receptor signaling pathway to promote proliferation.Our results suggest that, LPA3 receptor can be a potential target for ovarian cancer treatment.