关键词: 卵巢癌, 基质金属蛋白酶-9（MMP-9）, Toll样受体（TLRs）, 肿瘤相关巨噬细胞（TAM）

Abstract: Objective To investigate the influence of M2-type macrophage on expression of matrix metalloproteinase 9(MMP-9) in ovarian cancer cell, and to analyze the underlying mechanism about Toll-like receptors signaling pathway. Methods 320nM PMA was added to induce THP-1 cell into M2-type macrophage in vitro. M2-type macrophage and SKOV3 non-contacting co-culture model was established by Transwell method. After the co-cultrue process of 12 and 24 h, TLR1, 2, 6 and MMP-9 mRNA were detected by Real-time PCR. MyD88, TRAF6, and P-NF-κB and MMP-9 expression level were evaluated by Western blot. Testing the expression of MMP-9 after SKOV3 was stimulated with TLR1, 2 and 6 agonist for the time of 6, 12 and 24 h respectively. Results Type M2 macrophages could be induced differentiation by PMA. After the co-culture process of 24 and 48 h, MMP-9 mRNA and protein relative expressions in SKOV3 cells were significantly higher (P<0.05). The content of TLR1, 2 and 6 mRNA was highly expressed in SKOV3 (P<0.05). Co-cultured after 24 and 48 h, TLRs signaling pathway proteins MyD88, TRAF6, and P-NF-κB have synchronous increased expression in SKOV3(P<0.05). TLR1, 2 and 6 agonist respectively stimulated SKOV3 for 6 h, 12 h, 24, MMP-9 mRNA level had a significantly high expression (P<0.05). Conclusion Polarization-type tumor-associated macrophage could promote MMP-9 expression in ovarian cancer cells, and its mechanism is possibly though stimulating and activation of TLRs signaling pathway, which is closely connected with invasion and metastasis of ovarian cancer.

Key words: ovarian cancer, matrix metalloproteinase 9, Toll-like receptors, Tumor associated macrophage