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

Published on Dec 1, 2019in Molecular Cancer Therapeutics5.615
· DOI :10.1158/1535-7163.MCT-19-0118
Guannan Zhao9
Estimated H-index: 9
(UTHSC: University of Tennessee Health Science Center),
Qinghui Wang9
Estimated H-index: 9
(UTHSC: University of Tennessee Health Science Center)
+ 9 AuthorsJunming Yue34
Estimated H-index: 34
(UTHSC: University of Tennessee Health Science Center)
Sources
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.
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