Accession Number : ADA589152


Title :   Nuclear Factor-Kappa B Activity in the Host-Tumor Microenvironment of Ovarian Cancer


Descriptive Note : Annual rept. 25 July 2012 24 July 2013


Corporate Author : VANDERBILT UNIV NASHVILLE TN


Personal Author(s) : Wilson, Andrew


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a589152.pdf


Report Date : Aug 2013


Pagination or Media Count : 87


Abstract : Overcoming tumor resistance to platinum chemotherapy is critical for prolonging life in women with advanced ovarian cancer. The nuclear factor-kappaB (NF- B) signaling pathway is a key mediator of tumorigenesis by linking inflammatory pathways to cancer. Inhibitors of NF- B such as thymoquinone (TQ) potentiate the effects of cytotoxic agents, including cisplatin, in ovarian cancer cells. Equally relevant are the potential effects of NF- B inhibition in host cells such as peritoneal macrophages, thought to play pro-tumor (M2-like) or anti-tumor (M1-like) roles during ovarian cancer progression. We will define patterns of NF- B activity in host cells using NF- B reporter (NGL) transgenic mice injected with mouse ID8 ovarian cancer cells. NF- B activity in tumor cells will be monitored through stable transfection of the NGL reporter. We have detected increased NF- B reporter activity in tumor cells and in host macrophages, and increased markers of M2 macrophages in ascites fluid, in late stages of progression. Reducing NF- B activity in tumor cells with TQ treatment was associated with a shift towards M1 macrophages, while longer-term TQ treatment lead to increased ascites, elevated NF- B signaling and an M2 shift. Combined TQ and cisplatin treatment lead to synergistic anti-tumor effects in vitro, reduced tumor burden and apoptotic marks in tumors to a greater extent than treatment with cisplatin alone, and reduced M2, and induced M1, macrophage markers.


Descriptors :   *OVARIAN CANCER , CELLS(BIOLOGY) , CHEMOTHERAPY , MACROPHAGES , NEOPLASMS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE