PT  - JOURNAL ARTICLE
AU  - CHEN, LI-KUEI
AU  - CHEN, SHIOU-SHENG
AU  - SHIH, CHIEN-HUNG
AU  - HUANG, ZI-XUAN
AU  - CHEN, LINYI
AU  - CHEN, KUEN-BAO
TI  - Ketamine Promoted Breast Cancer Invasion and Metastasis Through Up-regulating Wnt, BMP, and EGFR Signaling
AID  - 10.21873/anticanres.16745
DP  - 2023 Dec 01
TA  - Anticancer Research
PG  - 5415--5424
VI  - 43
IP  - 12
4099  - http://ar.iiarjournals.org/content/43/12/5415.short
4100  - http://ar.iiarjournals.org/content/43/12/5415.full
SO  - Anticancer Res2023 Dec 01; 43
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.