The Use of a REV-ERB Synthetic Agonist for T Helper 17-Based Cancer Therapy

Researchers have titled chronic inflammation the “hallmark of cancer,” due to its key role in inducing nearly twenty percent of the malignancies worldwide. Chronic inflammation exists for an extended period, gradually creating the right enviroment in which cancer can thrive. Chronic inflammation causes damage to cell DNA and alters the way cells replicate and divide; this damages healthy tissue and promotes cancerous tumor growth. T Helper 17 (Th17) cells are a subset of T cells known to play a key role in driving inflammation. Th17 cells tend to accumulate within the tumor microenvironment. While their role in tumorigenesis is complex, they promote tumor growth in many cancer types. REV-ERBs are a class of nuclear hormone receptors that was recently identified as a modulator of Th17 cell development. This experiment demonstrates that the use of a REV-ERB agonist reduces inflammation through the Th17 molecular network. We used qPCR to test the effects of a REV-ERB agonist on the relative expression of genes associated with Th17 cell differentiation and resulting inflammation. We used samples of mouse microglial cells (BV2 cells) cultured in a variety of conditions. When cultured in the presence of lipopolysaccharides (LPS), bacterial toxins, BV2 cells undergo an inflammatory response. The BV2 cells co-treated with LPS and a REV-ERB agonist expressed these genes (Il-10, Il-1β, Il-6, Ccl2, Cox-2, Tnfα) to a lesser extent than the BV2 cells treated with LPS alone; thus, the REV-ERB agonist counteracted the effect of the LPS. These results indicate that REV-ERB agonists are worthy of future research into their utility as a means of cancer prevention and treatment.