Abstract 241: Vimentin offers a potential target for the prevention of ovarian tumor progression and recurrence

Abstract

Abstract Background: Aggressive rates of progression and frequent recurrence are the main causes of high rates of death due to ovarian cancer (OVCA). Vimentin, an intermediate filament protein, expressed by ovarian mesenchymal cells may be involved in OVCA metastasis and recurrence. Ashwagandha (Withania somnifera, ASH, a natural product) has shown to improve tumor-associated stress against several malignancies. Objectives: The goals of this study were to examine whether (1) OVCA progression is associated with vimentin expression; and whether (2) OVCA progression and vimentin expression can be prevented by dietary supplementation of Ashwagandha (ASH) in laying hen model of spontaneous OVCA. Methods: Exploratory study: Clinical specimen from normal ovaries (n=10), benign tumors (n=5) and malignant ovarian epithelial cancers at early (n=7) and late stages (n=16) were collected from patients and examined for vimentin expression. Prospective study: 4-year old laying hens with normal ovaries or ovaries with early stage OVCA were supplemented with 2% dietary ASH root powder or basal diet (24 hens in each group containing 18 healthy, 6 with early stage OVCA). Hens were provided with feed and water ad libitum for 120 days and euthanized thereafter. Tumor stages were recorded; serum, normal or cancer ovaries were collected. Expression of vimentin both in clinical and preclinical treated or untreated specimens was examined. Statistical differences in the intensity of vimentin expression among different pathological and ASH supplemented groups were determined using ANOVA and t-tests. Results: Vimentin was localized in the nucleus and cytoplasm of normal ovarian, benign and malignant cells. Compared with normal and benign tumors, the intensity of vimentin expression was significantly (P<0.0001) lower in early stage OVCA and increased remarkably in late stage OVCA. Similar to OVCA patients, intensity of vimentin expression was lower in hens with early OVCA than normal hens, and increased significantly (P<0.0001) in hens with late stage OVCA. As compared with untreated hens, tumor incidence and progression as well as vimentin expression decreased significantly in hens treated with 2% dietary ASH. Conclusions: Results of the present study suggest that vimentin expression increased during tumor metastasis. ASH treatment reduced OVCA metastasis by inhibiting vimentin expression. Therefore, vimentin may represent a potential target for ASH to prevent OVCA progression and metastasis. Support: Support: R21CA187309-02. Citation Format: Aparna Yellapa, Janice M. Bahr, Sameer Sharma, Pincas Bitterman, Sanjib Basu, Animesh Barua. Vimentin offers a potential target for the prevention of ovarian tumor progression and recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 241. doi:10.1158/1538-7445.AM2017-241