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

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.

Author

• Cai, Yihua

Language

• en

Keyword

• ovarian cancer
• apoptosis
• resistance
• janus kinase
• cisplatin

Date created

• 2016

Type of Work

• Master's Thesis

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Biochemistry and Molecular Biology

Degree

• M.S.

Advisor

• Zhu, Wenge

Committee Member(s)

• Han, Zhiyong

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/0r967374w