Therefore, we picked these five miRNAs for even further confirmation

As shown in Figure 7, either AG1478 or WEB2086 could inhibit tumor growth compared with the control group. Compared with those two treat ments, the combination of AG1478 and WEB2086 led to the most significant inhibition of tumor growth at day 21 post treatment. The combined treatment of the two drugs was well tolerated, ARN-509 構造 as no obvious side effects were observed in the mice treated with AG1478 andor WEB2086. Discussion The observation that elevated levels of growth factor re ceptors are associated with adverse cancer outcomes has led to the development of approaches that specifically interrupt these autocrine pathways. The constitutive ac tivation of EGFR has been reported in various cancers, including breast, prostate, and ovarian cancers.<br><br> EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors have been approved for use in cancer patients. Despite these promising preclinical results, the inhib ition of EGFR, has resulted in limited antitumor effects when tested as a monotherapy in clinical settings. The PAFPAFR signaling axis has emerged as an im portant determinant of aggressive phenotypes AUY922 構造 in several malignancies. PAF has been associated with early malignant transformation in BRCA1 mutant epithelial ovarian cells, and melanocytic tumorigenesis has been observed in transgenic mice overexpressing PAFR. The many effects of PAF in tumors, such as in creased vascular permeability, the induction of neoan giogenesis, and the activation of metalloproteinases, have reinforced the concept that PAF promotes tumor metastasis.<br><br> Recent experiments have shown that the PAFR antagonist WEB2086 inhibits tumor growth in a murine melanoma model, improving overall survival when combined with chemotherapy. ALK 阻害剤 Studies on WEB2086 have primarily been performed with leukemia cells that were induced to undergo differen tiation andor apoptosis. WEB2086 has been proven to possess the ability to abrogate PAF mediated signals and exerts a wide anticancer activity capable of significantly decreasing proliferation in human solid tumor cells of dif ferent histogeneses and with a much higher efficacy than in normal cells. In addition, earlier experiments from our group have shown that the activation of PAFR has pleio tropic effects on tyrosine phospho EGFRSrcPaxillin in ovarian cancer.<br><br> Therefore, we hypothesized that there would be crosstalk between the PAFR and EGFR path ways, which may be one of reasons for the resistance of cancer cells to drugs, and that the combined targeting of PAFR and EGFR would synergistically inhibit ovarian can cer progression. In this study, we evaluated for the first time the antitu mor effects of PAFR and EGFR targeting strategies in ovarian cancer cell lines using the PAFR antagonist WEB2086 and EGFR inhibitor AG1478. In our in vitro and in vivo studies, we demonstrated that EGFR and PAFR were overexpressed in ovarian cancer cell lines, which led us to speculate that simultaneously targeting PAFR and EGFR may be a more effective therapeutic strategy than targeting either signaling pathway alone. Our results show that the combined inhibition of PAFR and EGFR additively inhibited ovarian cancer progres sion.