JQ1 inhibits tumour growth in combination with cisplatin and suppresses JAK/STAT signalling pathway in ovarian cancer. (February 2020)

• Record Type: Journal Article
• Authors: Bagratuni, Tina; Mavrianou, Nefeli; Gavalas, Nikolaos G.; Tzannis, Kimon; Arapinis, Calliope; Liontos, Michael; Christodoulou, Maria I.; Thomakos, Nikolaos; Haidopoulos, Dimitrios; Rodolakis, Alexandros; Kastritis, Efstathios; Scorilas, Andreas; Dimopoulos, Meletios A.; Bamias, Aristotle
• Is Part Of: European journal of cancer. Volume 126(2020)
• Page Start: 125
• Page End: 135
• Publication Date: 2020-02
• Subjects: JQ1 -- BRD4 -- c-Myc -- Ovarian -- JAK/STAT; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2019.11.017
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Overexpression of c-Myc is commonly seen in human ovarian cancers, and this could be a potentially novel therapeutic target for this disease. JQ1, a selective small-molecule BET (Bromodomain and extraterminal domain family) bromodomain (BRDs) inhibitor, has been found to suppress tumour progression in several cancer cell types. Results: Using a panel of ovarian cancer cell lines and primary cell cultures from human ovarian cancer ascites, we demonstrated that JQ1 significantly suppressed cell proliferation and induced apoptosis in an ovarian cancer cell by targeting BRD4 and c-Μyc. In addition, JQ1 sensitized ovarian cancer cells to cisplatin, the most commonly used chemotherapeutic agent in ovarian cancer. Importantly, this effect was observed in ovarian cells, which exhibited resistance to cisplatin alone. Finally, we show that JQ1 interacts with the JAK-STAT signalling pathway, a pathway important in supporting ovarian cancer cell survival by suppressing or inducing genes involved in cell survival and apoptosis, respectively. Conclusion: Our data, taken together, suggest that JQ1 is an attractive antitumour candidate for further investigation in the treatment of ovarian cancer, as it associates with cell proliferation, apoptosis, and alterations in the JAK-STAT signalling pathway, especially in patients with a platinum-resistant profile or in patients with relapsed disease. Highlights: JQ1 suppresses cell survival and induces apoptosis in ovarian cancer by targeting BRD4 and c-Μyc. JQ1 demonstrates antisurvival effects in ovarian cells, which exhibit resistance to cisplatin. JQ1 interacts with JAK-STAT pathway by differentiating genes involved in survival and apoptosis.