Gefitinib enhances sensitivity of endometrial cancer cells to progestin therapy via dual-specificity phosphatase 1
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Yuan Yang1,2,*, Jingyi Zhou1,*, Xiaoping Li1, Lijun Zhao1, Yuan Cheng1, Yanying Lin1, Jiaqi Wang1, Lihui Wei1, Yafeng Dong3 and Jianliu Wang1
1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, China
2The First Hospital of Lanzhou University, Lanzhou, China
3Obstetrics and Gynecology Department, University of Kansas School of Medicine, Kansas City, KS, USA
*These authors have contributed equally to this work
Jianliu Wang, email: firstname.lastname@example.org
Keywords: endometrial cancer; gefitinib; MPA; DUSP1; targeted therapy
Received: July 14, 2017 Accepted: December 01, 2017 Published: December 15, 2017
In this study, we investigated if Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, augments endometrial cancer (EC) therapy with medroxyprogesterone acetate (MPA). Combined treatment with Gefitinib plus MPA decreased the proliferation and invasiveness of the Ishikawa and RL952 EC cell lines more effectively than MPA treatment alone. Moreover, combined treatment with Gefitinib plus MPA reduced growth of EC xenografts in Balb/c nude mice more than either Gefitinib or MPA alone. The therapeutic efficacy of combined Gefitinib plus MPA treatment was dependent on expression of dual-specificity phosphatase 1 (DUSP1). DUSP1 knockdown in Ishikawa cells treated with Gefitinib plus MPA showed greater proliferation and invasiveness than parental Ishikawa cells treated similarly. EC cells treated with the combination of Gefitinib plus MPA also showed DUSP1-dependent reductions in phospho-ERK1/2 and increases in E-Cadherin. Thus, Gefitinib appears to DUSP1-dependently enhance the therapeutic efficacy of progestin in EC cells.
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