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Data from Silencing Survivin Splice Variant 2B Leads to Antitumor Activity in Taxane-Resistant Ovarian Cancer
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Data from Silencing Survivin Splice Variant 2B Leads to Antitumor Activity in Taxane-Resistant Ovarian Cancer
Data from Silencing Survivin Splice Variant 2B Leads to Antitumor Activity in Taxane-Resistant Ovarian Cancer
PV
Pablo E. Vivas-Mejia
Pablo E. Vivas-Mejia
CR
Cristian Rodriguez-Aguayo
Cristian Rodriguez-Aguayo
HH
Hee-Dong Han
Hee-Dong Han
MS
Mian M.K. Shahzad
Mian M.K. Shahzad
FV
Fatma Valiyeva
Fatma Valiyeva
MS
Mineko Shibayama
Mineko Shibayama
AC
Arturo Chavez-Reyes
Arturo Chavez-Reyes
AS
Anil K. Sood
Anil K. Sood
GL
Gabriel Lopez-Berestein
Gabriel Lopez-Berestein
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6519623
Abstract
Purpose: To study the role of survivin and its splice variants in taxane-resistant ovarian cancer.Experimental Design: We assessed the mRNA levels of survivin splice variants in ovarian cancer cell lines and ovarian tumor samples. siRNAs targeting survivin were designed to silence all survivin splice variants (T-siRNA) or survivin 2B (2B-siRNA) in vitro and orthotopic murine models of ovarian cancer. The mechanism of cell death was studied in taxane-resistant ovarian cancer cells and in tumor sections obtained from different mouse tumors.Results: Taxane-resistant ovarian cancer cells express higher survivin mRNA levels than their taxane-sensitive counterparts. Survivin 2B expression was significantly higher in taxane-resistant compared with -sensitive cells. Silencing survivin 2B induced growth inhibitory effects similar to silencing total survivin in vitro. In addition, survivin 2B-siRNA incorporated into DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) nanoliposomes resulted in significant reduction in tumor growth (P < 0.05) in orthotopic murine models of ovarian cancer, and these effects were similar to T-siRNA-DOPC. The antitumor effects were further enhanced in combination with docetaxel chemotherapy (P < 0.01). Finally, we found a significant association between survivin 2B expression and progression-free survival in 117 epithelial ovarian cancers obtained at primary debulking surgery.Conclusions: These data identify survivin 2B as an important target in ovarian cancer and provide a translational path forward for developing new therapies against this target. Clin Cancer Res; 17(11); 3716–26. ©2011 AACR.
Keywords
CELL DEATH
OVARIAN CANCER
ANTITUMOR
SURVIVIN 2B
ORTHOTOPIC MURINE
MRNA LEVELS
2B SIRNA
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Open Access