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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway

Authors: Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nyuyen, Imelda Mercado-Uribe, Mei Yang, Juan Zou, Qintong Li, Jianguo Xiao, Bin Chang, Guangzhi Liu, He Wang, Jinsong Liu

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer.

Methods

The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells.

Results

Western blot analysis indicated increased expression of the anti-apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins Bax, Bad, and Bid in HOC-7/IĸBαM cell. Further investigations validate this conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro-apoptotic effect by activating mitogen-activated protein kinase (MAPK) phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed that injection of HOC-7 induced subcutaneous tumor growth, which was completely regressed within 7 weeks. In comparison, HOC-7/IĸBαM cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by IĸBαM promoted sustained tumor growth and delayed tumor regression in HOC-7 cells.

Conclusion

Our results demonstrated that NF-kB may function as a tumor suppressor by facilitating regression of low grade ovarian serous carcinoma through activating pro-apoptotic pathways.
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Metadata
Title
Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway
Authors
Xue Xiao
Gong Yang
Peng Bai
Shunping Gui
Tri M. Bui Nyuyen
Imelda Mercado-Uribe
Mei Yang
Juan Zou
Qintong Li
Jianguo Xiao
Bin Chang
Guangzhi Liu
He Wang
Jinsong Liu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2617-2

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