College of Medicine, China Medical University, Taichung, Taiwan.
Department of Anesthesiology, China Medical University Hospital, Taichung, 40447, Taiwan.
Invest New Drugs. 2022 Dec;40(6):1165-1172. doi: 10.1007/s10637-022-01291-x. Epub 2022 Aug 9.
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.
氯胺酮在台湾被用作摇头丸的掺杂物而非医疗用途比安非他命更为普遍。氯胺酮对免疫抑制的作用可能在肿瘤生长中发挥某些功能作用，而氯胺酮滥用是否会增加肿瘤生长仍存在争议。本研究旨在探讨氯胺酮成瘾对乳腺癌及相关基因表达的影响。研究了氯胺酮处理对三阴性乳腺癌细胞系 EO771 的增殖、集落形成、迁移和侵袭的影响。此外，通过腹腔注射（IP）氯胺酮在小鼠中建立了氯胺酮成瘾模型，用于研究氯胺酮成瘾对肿瘤生长的影响及其可能的机制。在体外研究中，不同浓度的氯胺酮处理不会影响 EO771 细胞的增殖和集落形成。但氯胺酮确实增强了 EO771 细胞的迁移和侵袭。体内实验表明，与生理盐水组相比，氯胺酮成瘾小鼠的乳腺肿瘤体积和重量明显增加。与对照组相比，氯胺酮成瘾小鼠肿瘤中的 miR-27b-3p 水平、人表皮生长因子受体 2（HER2）和表皮生长因子受体（EGFR）显著增加。体内证据表明，氯胺酮可能会增加肿瘤微环境中的肿瘤生长，而 miR-27b-3p、HER2 和 EGFR 可能在该过程中发挥作用。
