Dual influence of TNFα on diverse in vitro models of ovarian cancer subtypes. Issue 2 (February 2021)

• Record Type: Journal Article
• Authors: Kocbek, Vida; Imboden, Sara; Nirgianakis, Kostantinos; Mueller, Michael; McKinnon, Brett
• Is Part Of: Heliyon. Volume 7:Issue 2(2021)
• Publication Date: 2021-02
• Subjects: Serous -- Clear cell -- Endometrioid -- Ovarian cancer -- Inflammation -- TNFα -- Epithelial; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2021.e06099
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: Ovarian cancer is the most lethal gynecological cancer. Numerous subtypes exist, each with distinct risk factors and prognosis. What underlies these subtypes and their progression is not clear, although inflammation through NFκB may play a key role. We performed a study on a series of well-characterized in vitro ovarian cancer models including TOV21G, TOV112D and OV90 originally derived from clear cell, endometrioid and high grade serous carcinoma respectively. Cells were treated with 0–100 ng/ml TNFα over 6–72 h. The NFκB pathway was inhibited by a series of NFκB pathway inhibitors, 100μM PDTC, 1μM PS-1145 and 200nM TPCA and the influence on cellular viability and inflammation was measured via an MTS assay and qPCR respectively. TNFα stimulation of NFκB was confirmed via Western blot. We found TNFα facilitated continued growth of TOV21G and TOV112D cells in an NFκB independent method. In contrast, TNFα inhibited OV90 cell growth in an NFκB dependent manner. TNFα stimulated production of IL-6, IL-8, MCP-1 and RANTES on all three cells lines, but only IL-6 and IL-8 were via NFκB mediated mechanisms. These results indicate TNFα may have diverse effects mediated through both NFκB and non-NFκB pathways on ovarian cancer cells. Understanding the role for TNFα in each subtype may have significant implications for charting disease progression and designing personalized treatments. Abstract : Serous, Clear cell, Endometrioid, Ovarian cancer, Inflammation, TNFα, Epithelial