Ketamine promotes breast tumor growth in a mouse breast tumor model involving with high expression of miR-27b-3p and EGFR

• Published in: Investigational new drugs Vol. 40; no. 6; pp. 1165 - 1172
• Main Authors: Chen, Li-Kuei, Shih, Chien-Hung, Chen, Shiou-Sheng, Huang, Zi-Xuan, Chang, Yu-Jung, Chen, Linyi, Chuang, Tsung-Hsien, Chen, Kuen-Bao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2022; Springer Nature B.V
• Subjects: Addictions; Amphetamines; Breast cancer; Cell proliferation; Colonies; Epidermal growth factor; Epidermal growth factor receptors; ErbB-2 protein; Growth factors; Immunosuppression; Ketamine; MDMA; Medicine; Medicine & Public Health; Oncology; Pharmacology/Toxicology; Receptors; Tumor microenvironment; Tumors; miR-27b-3p; Ketamine; Breast cancer biomarker; Epidermal growth factor receptor
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-022-01291-x

Summary Non-medical use of ketamine as an adulterant to ecstasy is more prevalent than amphetamine in Taiwan. Ketamine’s effect on immunosuppression might play some functional role in tumor growth, while it is still controversial whether ketamine abuse could increase tumor growth or not. This study aimed to investigate the influence of ketamine addiction in breast tumors and related gene expressions. The effect of ketamine treatment on proliferation, colony formation, migration, and invasion of triple-negative breast cancer cell line EO771 was examined. In addition, a ketamine addiction mice model was established by intraperitoneal injection (IP) of ketamine in mice and used to investigate the effects of ketamine addiction on tumor growth and the possible mechanisms. In the in vitro studies, ketamine treatment at different concentrations did not affect EO771 cell proliferation and colony formation. But ketamine did enhance migration and invasion of EO771 cells. The in vivo experiments showed significantly increased breast tumor volume and weight in ketamine-addicted mice than in normal saline groups. miR-27b-3p level, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) significantly increased in tumors of ketamine addiction mice compared to control mice. In vivo evidence showed that Ketamine might increase tumor growth on the tumor microenvironment, and miR-27b-3p, HER2, and EGFR might play a role in the process.