RT Journal Article SR Electronic T1 Ketamine Promoted Breast Cancer Invasion and Metastasis Through Up-regulating Wnt, BMP, and EGFR Signaling JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 5415 OP 5424 DO 10.21873/anticanres.16745 VO 43 IS 12 A1 CHEN, LI-KUEI A1 CHEN, SHIOU-SHENG A1 SHIH, CHIEN-HUNG A1 HUANG, ZI-XUAN A1 CHEN, LINYI A1 CHEN, KUEN-BAO YR 2023 UL http://ar.iiarjournals.org/content/43/12/5415.abstract AB Background/Aim: In this study, we used an orthotropic breast cancer model combined with ketamine addiction and next-generation sequencing (NGS) to comprehensively investigate molecular alterations in ketamine-mediated metastasis. Ketamine is widely used in anesthesia and drug abuse. Our previous study revealed that ketamine promotes the growth of breast cancer cells; however, the detailed molecular mechanism remains unknown. Materials and Methods: An orthotropic breast cancer model was established by injecting EO771 breast cancer cells into the mammary fat pad of mice intraperitoneally administered ketamine (30 mg/kg, daily) for 68 days. Tumors collected at day 38 were frozen for future analysis, and their metastasis state was checked at day 68. Results: Tumors were grouped and subjected to NGS analysis, followed by differential gene expression analysis (DEseq) and pathway identification. DEseq analysis showed that ketamine up-regulated metastasis-related signaling, and the key genes were BMP5, FZD6, MMP1B, EGFR, WNT5A, BMP7, and DCN. Conclusion: Ketamine addiction up-regulates the expression of genes involved in the Wnt, EGFR, and BMP signaling cascades, which may be associated with breast cancer progression and metastasis.