Abstract 23: Caloric restriction slows tumor growth and metastases in both hormone-sensitive and hormone-resistant prostate cancers

Abstract

Introduction: The purpose of this study is to assess the effect of caloric restriction (CR) on prostate cancer (PCa) tumor burden, proliferation, and overall survival with and without radiation treatment (RT). Additionally, we determined if the beneficial effect of CR noted are due to a reduction in pro-inflammatory markers hypothesized to enhance PCa tumorgenesis. Methods: To assess the effect of CR in vivo, 40 male 12 week-old NCRNu-M mice were injected with LNCaP or PC3 tumor cells. Once tumors were palpable, mice were randomly assigned to one of four treatment groups in cohorts of 10: ad libitum (AL) diet, 6.5Gy of radiation (RT), 30% reduction in caloric intake (CR), or CR+RT. Tumor growth and proliferation rate were measured 3 times per week via calipers and live bioluminescent imaging. Additionally, PCa tumor tissue were analyzed to determine if CR can exert its effect on tumor growth and metastases via IGF-1R signaling pathway. Results: Adding CR to RT decreased tumor progression. In the PC3 murine model, when compared to AL, RT reduced tumor size by 22%, 77% with CR, and 80% with CR+RT. In the LNCaP murine model, compared with AL, CR reduced tumor size by 49% and a 55% reduction with CR+RT. Primary tumor formation began 9 weeks post tumor injection in the radiated cohort and was delayed to 15 weeks post tumor injection in the CR and CT+ RT cohorts. Additionally, time to metastasis was delayed with CR (86 days to metastasis in AL, 93 with RT, and 108 when combining CR+RT). Molecularly, CR decreased multiple members of the IGF-1R signaling pathway. The total IGF-1 and IGF-1R levels exhibited 50% reduction with CR and CR+RT but total INSR levels. CR also induced a significant decrease of pGSK3β and pAKT levels. Conclusions: For the first time, we have shown that decreasing calories by 30% in both hormone-sensitive and hormone-refractory prostate cancer models, enhance the efficacy of radiation. Our experiments show that even CR alone and in combination with RT can improve PCa tumor proliferation rate, tumor burden, time to metastasis, and overall survival. We hypothesize that these changes are in part, due to the decrease of the IGF-1R signaling pathway. We propose that CR may be used as a novel therapeutic intervention to enhance outcomes of radiation treatment by altering the molecular profile of prostate tumors. Citation Format: Robert S. Gitman, Meredith LaRose, Edouard J. Trabulsi, Ajay Palagani, Tiziana DeAngelis, William K. Kelly, Leonard G. Gomella, Nicole L. Simone. Caloric restriction slows tumor growth and metastases in both hormone-sensitive and hormone-resistant prostate cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 23.