Abstract 3006: A novel strategy of targeting opioidergic receptors to potentially reduce human breast cancer cell proliferation, colony formation, invasion, and migration

Abstract

Abstract Breast cancer is the second most prevalent cancer after lung cancer among American women. The efficacy of current antitumor therapies is still quite limited. Endogenous opioid peptides, such as endorphin, which is involved in body stress controlling mechanisms, have been shown to enhance immune function and prevent cancer growth and progression in various animal models of cancers. Therefore, targeting the endogenous opioid peptides receptors in the regulation of cancer chemoprevention may offer new promise for the design of therapeutic strategies. Our previous studies have shown differential actions of mu-opioid receptor (MOR) and delta opioid receptor (DOR) on various cell types. In this study we tested the effects of a MOR antagonist naltrexone (NTX) and a DOR agonist (D-Ala2-,N-Me-Phe4,Gly-ol Enkephalin; DPDPE) on proliferation and invasion of human breast cancer cells of different molecular subtype such as T47D (Luminal A), MDA-MB-231 (triple negative, Claudin-Low) and MDA-MB- 468 (triple negative, basal A) in cultures. We used cytotoxicity, clonogenic, cell migration and cell invasion assays to identify effects of these drugs on cancer cells. We found that both NTX and DPDPE have significant cytotoxic effects on these breast cancer cells. Our work from clonogenic, cell migration and cell invasion assays showed that both NTX and DPDPE inhibit the formation of colony, migration and invasion of cancer cells in a concentration-dependent manner. These data suggest that naltrexone and DPDPE have anticancer efficacy in subtypes of human breast cancer cells. The anticancer effects varied depending on the concentration of the drugs and the subtype of breast cancer cells. (Supported by NIH grant R01 CA20863201). Citation Format: Sengottuvelan Murugan, Vanisha Patel, Dipak K. Sarkar. A novel strategy of targeting opioidergic receptors to potentially reduce human breast cancer cell proliferation, colony formation, invasion, and migration [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 3006.