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Ovarian primary and metastatic tumors suppressed by survivin knockout or a novel survivin inhibitor

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Title: Ovarian primary and metastatic tumors suppressed by survivin knockout or a novel survivin inhibitor
Authors: Zhao, Guannan Browse this author
Wang, Qinghui Browse this author
Wu, Zhongzhi Browse this author
Tian, Xinchun Browse this author
Yan, Huan Browse this author
Wang, Baojin Browse this author
Dong, Peixin Browse this author →KAKEN DB
Watari, Hidemichi Browse this author →KAKEN DB
Pfeffer, Lawrence M Browse this author
Guo, Yuqi Browse this author
Li, Wei Browse this author
Yue, Junming Browse this author
Keywords: BIRC5 (survivin)
Lentiviral CRISPR/Cas9 nickasevector
ovarian tumor metastasis
epithelial to mesenchymal transition (EMT)
orthotopic ovarian cancer mouse model
survivin inhibitor MX106
Issue Date: Dec-2019
Publisher: American Association for Cancer Research (AACR)
Journal Title: Molecular Cancer Therapeutics
Volume: 18
Issue: 12
Start Page: 2233
End Page: 2245
Publisher DOI: 10.1158/1535-7163.MCT-19-0118
Abstract: Survivin, a member of the inhibitor of apoptosis (IAP) family, is upregulated in multiple cancers including ovarian cancer, but is rarely detectable in normal tissues. We previously reported that survivin promoted epithelial to mesenchymal transition (EMT) in ovarian cancer cells, suggesting that survivin may contribute to ovarian tumor metastasis and chemoresistance. In this study, we tested whether knockout or pharmacological inhibition of survivin overcomes chemoresistance and suppresses tumor metastasis. The genetic loss of survivin suppressed tumor metastasis in an orthotopic ovarian cancer mouse model. To pharmacologically test the role of survivin on ovarian tumor metastasis, we treated chemoresistant ovarian cancer cells with a selective survivin inhibitor MX106 and found that MX106 effectively overcame chemoresistance in vitro. MX106 inhibited cell migration and invasion by attenuating the TGFβ pathway and inhibiting EMT in ovarian cancer cells. To evaluate the efficacy of MX106 in inhibiting ovarian tumor metastasis, we treated an orthotopic ovarian cancer mouse model with MX106, and found that MX106 efficiently inhibited primary tumor growth in ovaries and metastasis in multiple peritoneal organs as compared to vehicle-treated control mice. Our data demonstrate that inhibition of survivin using either genetic KO or a novel inhibitor MX106 suppresses primary ovarian tumor growth and metastasis, supporting that targeting survivin could be an effective therapeutic approach in ovarian cancer.
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 董 培新

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