Abstract 3608: Identification of differentially expressed genes in 4T1 mice triple-negative mammary gland cancer during the early phase of combination treatment with indomethacin and radiation

Abstract

Abstract Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. In order to develop the most effective treatment against TNBC, we tested the effects of the combination treatment with indomethacin and radiation on TNBC utilizing a mouse experimental TNBC equivalent model. Seven weeks old BALB/c mice were implanted with 4T1 mice triple-negative mammary gland tumor cells on the right hind leg one week before the treatments started. Mice were divided into four groups treated with vehicle control, 6 Gy radiation, 30 mg/L (in water) indomethacin, or combination regime of 6 Gy radiation and 30 mg/L indomethacin. 6 Gy radiation was given to mice on Day 0 only while indomethacin was given to mice every day. Mice received the combination treatment with radiation and indomethacin showed a significant tumor growth delay at the end of the treatment regime (Day 30). We next elucidated if there are changes in biological pathways during the early phase of combination therapy (Day 3). Total RNAs isolated from the primary tumors were subjected to whole genome transcriptomic analyses (RNAseq). We identified a total of 58 genes with 2-fold changes in expression and p-value <0.05 differentially expressed among the treatment groups. Strikingly, the trend in expression levels of differentially expressed genes identified from the combination treatment group was opposite to that from the other two treatment groups. Results indicate that the effect of combination treatment with indomethacin and radiation is neither additive or synergistic. In addition, pathway core analyses revealed “Cancer” as the top associated disease, and “GABA Receptor Signaling and cAMP-Mediated Signaling” as the top canonical pathways among the treatment groups. In conclusion, our findings provided a detailed snapshot of the early events occur in mice subject to either single or combination treatment with indomethacin and radiation. Data will improve our understanding of the treatment responses of TNBC. We believe further time-course and transcriptomic studies may be beneficial for the new therapeutic strategies for TNBC. Citation Format: Robert Yuk Sing Cheng, Lisa Ridnour, Timothy Back, Debashree Basudhar, Stephen Anderson, Daniel McVicar, David Wink. Identification of differentially expressed genes in 4T1 mice triple-negative mammary gland cancer during the early phase of combination treatment with indomethacin and radiation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3608.