VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 1

Rachita Gupta, BS, OMS-II; J. Annelies Hayward-Smithey, BS, OMS-II; Riva Kelly, BS, OMS-II; Melissa Lipsmeyer, MS, PhD VCOM-Louisiana 7 INVESTIGATING THE FUNCTION OF THE BACTERIAL-DERIVED METABOLITE INDOLE-3-PROPIONIC ACID IN ENDOMETRIAL CANCER

Background: Endometrial cancer is the most common malignancy of the female reproductive tract and its incidence and mortality are rising. Obesity is the most common risk factor for the development of endometrial cancer and is thought to drive pathological transformation and proliferation of the endometrium by increasing circulating estrogen levels, hyperinsulinemia and inflammation. Recent evidence has suggested that obesity-driven dysregulation of the gut microbiome contributes to the metabolic perturbations observed in endometrial cancer. The gut bacteria-derived metabolite indole-3 propionic acid (IPA) has anti-inflammatory and glucose regulatory properties in various normal tissues and some cancer types. However, no studies have evaluated the effects of IPA on endometrial cancer. Objective: The goal of this study is to determine the potential protective effects of IPA on endometrial cancer cell proliferation and viability as well as the impact of IPA on insulin signaling and glucose uptake in endometrial cancer cells. Given that endometrial cancer is largely driven by excess estrogen and impeded by progestins, we will evaluate the effects of IPA on estrogen and progesterone signaling to determine if IPA can prevent estrogen-driven proliferation or enhance the inhibitory actions of progesterone.

Methods: For this study we are utilizing the well-differentiated human endometrial adenocarcinoma cell line, Ishikawa. This cell line retains expression of both estrogen and progesterone receptors, making it ideal to discover novel interactions between the gut microbiome and sex steroid receptor signaling. Because endometrial cancer pathogenesis is largely driven by obesity, we will be utilizing our in vitro model of obesity where cells are cultured in media conditioned by human adipocytes in order to mimic an obesogenic environment. The effects of IPA on cell viability will be assessed by MTT assay. QPCR and western blot analysis will be utilized to investigate the impact of IPA treatment on steroid hormone receptor and insulin signaling pathways. Mechanistic assays evaluating glucose uptake will also be performed to complement studies on insulin signaling. Results: Analyses from this study are currently underway and are to be determined. Conclusions: This study will offer novel insights between the intersection of female reproductive health and the gut microbiome. Importantly, these investigations will reveal possible mechanism by which a disturbed gut microbiome can contribute to pathogenic changes of not only tissues of the female

reproductive tract, but of other tissues. Future studies will evaluate the effects of IPA on normal human endometrial stromal cells for a comparative analysis. Collectively, these studies will highlight the importance of a healthy gut microbiome which can likely be achieved through diet and healthy lifestyle modifications and serve as a window of opportunity to mitigate the onset of endometrial carcinogenesis in high risk women with overweight/obesity.

19 2024 Via Research Recognition Day