Journal
BMC CANCER
Volume 16, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12885-016-2617-2
Keywords
Ovarian cancer; NF-kB; Pro-apoptosis; Tumor suppressor; IkB alpha M
Categories
Funding
- R01 grant from the National Institutes of Health [R01CA131183-01A2]
- ovarian cancer Specialized Programs of Research Excellence (SPORE) [IP50CA83638]
- Cancer Center Core grant from the National Cancer Institute [CA016672]
- Fund of the National Nature Science Foundations [81001159/81202387]
- Sichuan Province Science and Technology Plan Project [2013JY0013/2014JY0213]
- Scientific Research Foundation of Sichuan University [2013SCU04A22]
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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, IkB alpha M, 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/I kappa B alpha M 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/I kappa B alpha M cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by I kappa B alpha M 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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