Investigation of the effects of thymoquinone and cisplatin on cell migration and angiogenesis in an ovarian cancer cell line

Ovarian cancer is one of the most common gynecological malignancies with high mortality in women. The disease is often diagnosed at an advanced stage, and the development of resistance to platinum-based chemotherapies limits treatment efficacy. Cisplatin (Cis) is a widely used platinum-based chemotherapeutic agent in the treatment of ovarian cancer; however, its systemic toxicity and secondary resistance mechanisms highlight the need for new and more effective therapeutic strategies. In this context, the combination of natural bioactive compounds with chemotherapy has emerged as a promising approach. Thymoquinone (TQ), a major phytochemical compound derived from Nigella sativa, stands out with its anti-neoplastic, anti-inflammatory, and antioxidant properties. In this thesis study, the effects of TQ, Cis, and their combinations on the SKOV-3 ovarian cancer cell line were evaluated in vitro. The research particularly focused on molecular pathways related to angiogenesis and cell migration. The cytotoxic effects of TQ (0–1000 µM) and Cis (0–200 µM) were assessed at different doses and incubation times (24, 48, and 72 hours) using the MTT assay. Subsequently, the protein levels of angiogenesis markers (VEGF and VEGFR1) and invasion/migration markers (MMP-2 and MMP-9) were analyzed via Western blotting. The effects of single and combined treatments on cell viability, morphological alterations, and dose-time responses were comprehensively examined. The findings showed that TQ reduced VEGFR1 expression while increasing MMP-2 levels at higher doses. Cis treatment led to decreased expression of VEGFR1 and MMP-9. The most notable results were obtained with the combination treatments, where VEGFR1, MMP-2, and MMP-9 levels were suppressed, leading to significant inhibition of both angiogenesis and migration. In particular, sequential application for 48 hours revealed that pretreatment with TQ enhanced the cytotoxic effect of Cis, as demonstrated by the viability analysis. In conclusion, this study revealed that the combined use of TQ and Cis may exhibit synergistic antitumor effects on SKOV-3 cells and can suppress tumor progression at the molecular level. These findings support the potential of integrating natural compounds into conventional chemotherapy regimens to develop more effective and selective treatment strategies.