Ketamine inhibits colorectal cancer cells malignant potential via blockage of NMDA receptor

Experimental and Molecular Pathology
Wenming DuanYahua Liu

Abstract

Ketamine, a common N-methyl-d-aspartate receptor (NMDAR) antagonist, is an option for cancer pain treatment in clinical practice. Ketamine has been shown to have the capacity to attenuate cancer cells malignancy. However, the underlying mechanism remains elusive. In the present study, we reported that ketamine inhibited the malignant potential of colorectal cancer cells and investigated the possible mechanisms involved. Ketamine suppressed the expression of VEGF, HIF-1α, p-AKT, p-ERK, and p-CaMK II, and reduced intracellular Ca2+ level in a concentration dependent manner (1, 5, 10 μg/ml). Furthermore, AP5 and MK801 (NMDAR inhibitors), and KN93 (CaMK II inhibitor), decreased the expression of VEGF, HIF-1a, p-AKT, p-ERK, and p-CaMK II, which were similar to the effect of ketamine. Further, the anti-tumor effect of ketamine was reversed by d-serine (NMDAR activator). Ketamine did not affect NMDA receptor expression, however knockdown of NMDA receptor using siRNA attenuated the effect of ketamine on cell migration. Collectively, these findings demonstrated that ketamine attenuated the expression of VEGF and cell migration ability in colorectal cancer cells, probably via blockage of NMDA receptor.

Citations

Sep 13, 2019·Fundamental & Clinical Pharmacology·Yaojun LuShaoqiang Huang
Sep 15, 2020·Expert Opinion on Therapeutic Patents·Hazem AhmedSimon M Ametamey
Sep 15, 2020·Cancer Management and Research·Xiaoqing FanRuiting Wang
Sep 7, 2020·Molecular Biology Reports·Siqi DuDaniel W Armstrong
Feb 4, 2021·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Jin Sun ChoYoung-Lan Kwak
Jun 16, 2021·World Journal of Surgical Oncology·Zhixiu XiaHong Zhang
Oct 13, 2021·Pain Management·Maria F RamirezJuan P Cata

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