Electronic Thesis/Dissertation


Identify a Janus Kinase Inhibitor that Overcomes Cisplatin Resistance in Ovarian Cancer Open Access

Cisplatin is one of the most effective agents in treating ovarian cancer. However, cancer cells often develop resistance to cisplatin. Therefore, there is a search for new therapeutic agents and targets towards platinum resistance. To investigate therapy methods, we developed cisplatin resistant ovarian cell lines. We performed a HTS assay on over 5000 chemicals on cisplatin resistant ovarian cancer cells and, identified chemicals that can efficiently overcome cisplatin resistance. A Janus kinase inhibitor was identified to have synergistic effect combined with cisplatin. Janus-activated kinase can affect transcription, target cell cycle, cell proliferation, and cell apoptosis. In this study, JAK expression was found to be upregulated in cisplatin resistance cell lines, and depletion of JAK in resistant cells resensitized them to cisplatin. Moreover, JAK inhibitor can overcome cisplatin resistance in resistant ovarian cancer xenograft when combined with cisplatin. Therefore, we demonstrated that inhibition of Janus kinase is a strategy to treat cisplatin resistance of ovarian cancer.

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