Integrin-Linked Kinase Expression Increases With Ovarian Tumour Grade And The Crucial Role In Invasive Ability Of Human Ovarian Carcinoma Cell Lines

Integrin-linked kinase is a serine/threonine kinase that binds to the cytoplasmic domains ofβ1, andβ3 integrins and mediates the link between cell and extracellular matrix. Since the crucial role of ILK in transmiting intracellular and extracellular signals,as well as the cell cycle arrest and the initiation of cell apoptosis by suppressing the activity of ILK, ILK becomes an attractive target for tumor gene and medicine therapeutics.PI3K/AKT signal conduction is closely related to tumor occurrence and development. The activation of PI3K/AKT signal conduction pathway plays a crucial role in malignant tumor metastasis though some possible mechanism.As a PI3k kinase-dependent kinase, ILK transmits extracellular signals to the downstream by phosphorylation of its downstream targets-protein kinase B(PKB/AKT) and glycogen synthase kinase-3β(GSK-3β),and participates in the regulation of cell survival, proliferation, differentiation, adhesion, migration and so on.It is proved that 2-(4-morpholinyl)-8-phenyl chromone(LY294002) completely and specifically inhibit from the activity of PI3K/AKT. Here we assume that ILK is associated with the invasion and metastasis in human ovarian carcinoma, and the inhibition of PI3K/AKT signal conduction pathway can depress the expression of ILK, and then inhits the invasive ability of human ovarian carcinoma cell lines HO8910PM and HO8910.The objective of our experiment is to investigate the relationship between ILK expression and ovarian tumour Grade and its clinical significance, and to demonstrate the inhibitory effects of LY294002 on expression of ILK the role of ILK in the invasive ability of human ovarian carcinoma cell lines HO8910PM and HO8910.Methods: 104 specimens including normals (n=7), benign (n=20), borderline (n=16), carcinoma(n=43) were evaluated by immunohistochemistry staining (sp methods). The inhibitory effect of LY294002 on the expression of ILK in cell lines HO8910PM and HO8910 was analyzed using Immunocytochemical Method, Western-Blot and RT-PCR. The inhibitory effect of LY294002 on the growth of HO8910PM and HO8910 cell lines was measured by MTT assays. The cell adhesive ability of HO8910PM and HO8910 cell lines to matrigel was measured using MTT assay. The invasive ability of HO8910PM and HO8910 cell lines was assessed with a transwell cell culture chamber.Results: No immunoreactive ILK was observed in normal ovarian. There was significant difference among benign, borderline and carcinoma (P <0.05). In ovarian cancer,there was significant difference among clinical stageⅠ-Ⅱvs Ⅲ-Ⅳ(P<0.05), and was associated with low grade and lymph node metastasis (P <0.05). LY294002 inhibit the expression of ILK in HO8910PM and HO8910 celllines(P<0.05). The inhibitory effects were enhanced when increasing the concentration of LY294002. LY294002 can inhibit the growth and the invasive ability of human ovarian carcinoma cell lines HO8910PM and HO8910(P<0.05).Conclusion: ILK may serve as a useful marker of the biological behavior of ovarian tumors, and can provide useful information for invasion of ovarian tumor. The adhesive ability of ovarian carcinoma cell line with high expression of ILK was weaked, and the invasive ability was enhanced. This was probably due to the activation of PI3K/AKT signal transduction pathway. LY294002 suppresses the invasion of HO8910PM and HO8910 celllines via inhibiting the expression of ILK.