Verteporfinin TCAM-2 insan seminoma hücrelerinde kanser önleyici etkisinin belirlenmesi

Testicular cancer is the most common solid organ malignancy in young men. The Hippo pathway is a highly conserved signaling pathway with crucial roles in organ size, tissue homeostasis, and cancer development. Verteporfin is an inhibitor of Hippo pathway with promising roles in anticancer therapy. In the thesis study, we hypothesized that verteporfin may have anti-cancer effect on TCam-2 human seminoma cells. Therefore, the aim of the study was to investigate the effect of verteporfin treatment at different doses and concentrations on the proliferation, migration and apoptosis process in TCam-2 cells. Hippo signaling pathway protein expression in testis, embryonal carcinoma and seminoma tissues was determined by immunohistochemistry staining. TCam-2 cells were treated with different concentrations of verteporfin (1, 5, 10, 20 and 40 μM) for 24, 48 and 72 h. Protein and mRNA levels of Hippo pathway proteins, as well as their localization were investigated. Effect of verteporfin on cell migration, proliferation and apoptosis were also evaluated. In human testis, embryonal carcinoma and seminoma tissues, Hippo pathway proteins were detected as specifically and differentially localized. In vitro, as the duration and dose of verteporfin treatment increased, the level of the Hippo pathway proteins decreased, and mRNA levels remained unchanged. We also showed that Hippo signaling pathway proteins localized in the cell nucleus were translocated to cytoplasm depending on the increasing dose of verteporfin in TCam-2 cells. Verteporfin decreased the cell proliferation, migration and cell viability, as well as increased the apoptosis in TCam-2 human seminoma cells depending on the dose. In conclusion, we suggest that the Hippo pathway and verteporfin relationship may be a therapeutic target for seminoma by affecting cell proliferation, viability, migration and apoptosis processes. Further in vivo and in vitro studies are needed to better understand the underlying mechanism of seminoma and the role of Hippo pathway to earn new insights on the seminoma therapies. Key words: Human testis tissue, Seminoma, TCam-2, Hippo, Verteporfin.