Abstract 2505: Baicalein reverses chronic stress-induced ovarian cancer promotion through GABA receptors

Abstract

Abstract Studies suggest that chronic stress accelerate the progression of ovarian cancer, and the promotion effects can be abrogated by β-blockers. However, β-blockers should be assessed and tailored to each cancer patient as they will exert toxic effects in overdose. Baicalein, a widely used Chinese herbal medicine, identified as a new type of anticancer drug with an obvious function of anti-anxiety in animal experiments and whose mechanism may be mediated by GABA receptors. The focus of the current study was to determine whether baicalein could block the effects of chronic stress on tumor growth and investigate the underlying mechanism that relates to GABA receptors. Two kinds of ovarian cancer cell lines (OVCAR-8 and CAOV-3) were selected to be investigated in the inhibitory effect of baicalein on cancer cells. Cell CCK-8 assay, wound healing assay, transwell assay and flow cytometry were used for in vitro experiments. Chronic stress was induced by a restrained stress model in nude mice carrying xenografts in the presence and absence of treatment with baicalein. Xenograft sizes and weight were measured after 4 weeks. Norepinephrine was measured by HPLC and GABA was measured by immunoassays in blood and tumor tissues. Expression of GABA receptors in the xenografts was analyzed by real-time quantitative PCR, western blotting and immunohistochemistry (IHC). Our results showed that ovarian cancer cell lines exhibited significant promotion in the presence of NE concentrations of 10Μm and baicalein concentrations of 10μM could reverse its effects by Cell CCK-8 assay and wound healing assay. Daily restraint stress resulted in significantly increased tumor growth in tumor model of ovarian cancer in nude mice. And this increase was completely blocked with daily baicalein treatment. Chronic stress attenuated expression of GABA receptors in vivo and in vitro; conversely, baicalein increased expression of GABA receptors. Overall, our data suggest that baicalein stimulated GABA receptors activation to reduce tumor growth in ovarian cancer. Considering the stimulatory effects of chronic stress on cancer growth, our study implicates baicalein as a potential medicine for blocking the deleterious effects of chronic stress. Citation Format: Ke Li, Yu Kang, Yinhua Yu. Baicalein reverses chronic stress-induced ovarian cancer promotion through GABA receptors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2505.