Abstract 3845: 24R,25-Dihydroxyvitamin D3 reduces tumor burden and metastasis in ER+ breast cancer in vivo

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Abstract The purpose of this study was to investigate the effects of 24R,25-dihydroxyvitamin D3 (24,25), on tumor growth and metastasis in an in vivo estrogen receptor positive (ER+) orthotopic breast cancer model. 1α,25(OH)2D3 has been shown to have pro-apoptotic effects on breast cancer both in vitro and in vivo. 24,25, a naturally occurring metabolite, is present in human serum at concentrations up to 10 times higher than 1,25. Moreover, 1,25 regulates production of 24,25 by stimulating expression of the 24-hydroxylase. 6-8 week old female nod scid gamma IL2R mice were kept on an ad libitum vitamin D deficient diet. 15 days before surgery, mice were implanted with 1.7mg 0-order release estrogen (E2) pellets. In the first experiment, mice were given a fast-release pellet (45 days). In the second experiment, mice were given a slow-release (90 day) pellet. After 15 days of acclimation (day 0), mice were injected in the T4 mammary fat pad with 1M fluorescently labeled MCF7 cells (an ER+ breast cancer cell line) and cells in 50:50 PBS:Matrigel solution. Tumors were measured once a week starting at day 14 and tracked throughout the course of the study. On day 30, 24,25 treatment was initiated. Each experiment was divided into three groups: 0 ng 24,25, 25 ng 24,25, or 100 ng 24,25 per injection, with n=6-8 mice per group. Treatments were administered three times a week in a 50µL intraperitoneal injection. On day 70, mice were harvested and assessed for tumor burden and metastasis by fluorescence detection microscopy. Fluorescent tissues were marked ‘metastasis positive' and harvested for future immunohistochemical analysis. Mice that were given 24,25 three times weekly showed decreased tumor burden and metastasis as compared to controls. In the first experiment (45 day E2), 25ng and 100ng 24,25 treated mice had significantly lower relative tumor volumes than controls beginning on day 70. These 24,25 treated mice also showed significantly lower rates of left axial lymph node metastasis, and had statistically longer survival rates. The second experiment (90 day E2) had similar results. Mice treated with 25ng and 100ng 24,25 had decreased tumor burden as compared to 0ng controls on day 70. Mice given 24,25 had decreased lung metastasis; however, mice treated with 100ng 24,25 had increased rates of right axial lymph node metastasis. Altogether, mice in both groups that were treated with 100ng of 24,25 had decreased rates of left axial lymph node metastasis and lung metastasis as compared to controls, and statistically longer survival rates. Thus 24,25 could play a role in 1,25's anti-apoptotic effect on breast cancer, potentially via upregulation of 24,25. Citation Format: Anjali Verma, David Joshua Cohen, Chandana Muktipaty, Barbara D. Boyan, Zvi Schwartz. 24R,25-Dihydroxyvitamin D3 reduces tumor burden and metastasis in ER+ breast cancer in vivo [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 3845.