LPA promotes migration and invasion of human ovarian cancer cells through LPA receptors

【摘要】：Background: Lysophosphatidic acid(LPA),one of the active lysophospholipid(LP), is an important extracellular signal molecule. As a bioactive lipid,LPA can regulates several cellular functions critical for proliferation, survival, cytoskeletal reorganization, migration, invasion and cytokine production via G-protein coupled receptors EDG family(LPA1, LPA2, and LPA3) and perhaps non-EDG family(LPA4–6).This experiment found that LPAR1 and LPAR3 was highly expressed in the tumor cells in the human ovarian cancer cell on the research of tumor proliferation and metastasis, while the LPA had obvious promotes effect on the proliferation and metastasis of ovarian cancer cells. Therefore, LPA has been suggested as a biomarker for ovarian cancer. It is worthwhile to conduct deep exploration on whether the LPA can be developed into a drug to treat the ovarian cancer. Methods: Culture human ovarian cancer cells. Real Time PCR detect the LPAR expression in the human ovarian cancer cell. Detect the proliferation by MTT method. At the same time using Micro chemotaxis chamber method to test the effects of LPA on cell migration. Then interference LPAR1/3 detected A2780/HO-8910 cell proliferation and migration. Protein expression was detected by Western Blot. Results: The Real Time PCR result discovered that LPAR1/LPAR3 is higher than other receptors expression in the human ovarian cancer cell A2780/HO-8910. LPA can stimulate A2780/HO-8910 cells to proliferation and found a dose-dependent. At the same time we found that LPA can induce cell migration.. The Western Blot results display that LPA stimulate A2780 cell proliferation and migration induced mainly Gi proteins play a role in the process, and activate the downstream MAKA signaling pathways. Conclusions: LPA induces migration and proliferation of ovarian cancer cells A2780/HO-8910 through LPAR1/LPAR3/Gi//P38 and LPAR1/LPAR3/Gi/ERK respectively.