Abstract 3739: Characterization of the effects of DIM (3,3’-Diindolylmethane) on irradiated tumors and anti-tumor immunity

Abstract

Abstract The overall goal of this project is to determine the efficacy of DIM (3,3’-Diindolylmethane) to protect normal tissues during radiotherapy but not enhance the survival of irradiated tumors. We tested expression change of p53-downstream genes in the absence and presence of DIM after radiation exposure using hTERT-immortalized human mammary epithelial cells. Radiation-induced gene inductions for both p21 and Wip1 were found attenuated in cells pretreated with various concentrations of DIM compared to the vehicle control. To reveal DIM’s effects on the global transcriptome of irradiated cells, we performed whole genome gene expression microarray analysis. Pathway analysis results showed that the differentially expressed genes are involved in cell cycle, p53 network, DDR, and related pathways. Gene regulation pattern at the later post-radiation time point in the presence of DIM shows similarity with that of early time point with no DIM, which suggests that DIM treatment delays responses of cell-cycle-related genes. We monitored tumor growth after localized radiation in tumor xenograft models of MDA-MB-231 and HCC1937 human breast carcinoma cell lines using immunocompromised NSG mice. The fractionated regimen consists of a total dose of 24 Gy in four fractions (6 Gy per fraction given every other day) with administration of DIM or vehicle at one hour prior to each fraction. DIM showed no significant effect on the growth of irradiated tumors, i.e. DIM did not affect the treatment efficacy of radiation on tumors. To investigate effects of DIM on tumor microenvironment, we treated tumors with fractioned radiation in an E0771 syngeneic tumor model. DIM treatment enhanced tumor infiltration of lymphocytes population. These studies support the goal of developing DIM as a clinical radioprotector in order to improve the therapeutic index by allowing higher doses of radiation to improve local tumor control by reducing late dose-limiting normal tissue toxicity by radiation. Citation Format: Renxiang Chen, Lijun Li, Lorreta Yun-Tien Lin, Albert J. Fornace, Heng-Hong Li. Characterization of the effects of DIM (3,3’-Diindolylmethane) on irradiated tumors and anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3739.