Dexmedetomidine suppresses the progression of esophageal cancer via miR-143-3p/epidermal growth factor receptor pathway substrate 8 axis

Abstract

Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, transwell migration and invasion assays and Western blot assay. The expression of miR-143-3p was measured by quantitative real-time PCR in esophageal cancer tissues and cells. The binding sites between miR-143-3p and epidermal growth factor receptor pathway substrate 8 (EPS8) were predicted by Starbase online software, and the combination was verified by dual-luciferase reporter assay. The murine xenograft model was established using KYSE150 cells to verify the function of DEX in vivo . DEX inhibited the proliferation and metastasis while accelerated the apoptosis of esophageal cancer cells. The abundance of miR-143-3p was lower in esophageal cancer tissues and cells than that in paring normal tissues and normal esophageal mucosal cells Het-1A. MiR-143-3p could be induced by DEX treatment in esophageal cancer cells, and miR-143-3p also suppressed the development of esophageal cancer. EPS8 was a functional target of miR-143-3p, and it played an oncogenic role in esophageal cancer. DEX inhibited the growth of tumor via miR-143-3p/EPS8 in vivo . DEX suppressed the growth and metastasis while facilitated the apoptosis of esophageal cancer cells through upregulating the abundance of miR-143-3p and reducing the level of EPS8 in vivo and in vitro , providing promising target for the treatment of esophageal cancer.

Effect of Dexmedetomidine on Biochemical Recurrence in Patients after Robot-Assisted Laparoscopic Radical Prostatectomy: A Retrospective Study

“…It remains unclear whether dexmedetomidine affects the postoperative prognosis and outcomes in patients with all types of cancer. Recently, dexmedetomidine was reported to inhibit esophageal cancer progression via the miR-143-3P/epidermal growth factor receptor pathway substrate 8 in vivo [ 7 ]. Additionally, Owuso et al performed a retrospective study on patients who had undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and demonstrated that intraoperative and/or early postoperative continuous infusion of dexmedetomidine was not associated with survival [ 19 ].…”

“…The effects elicited by dexmedetomidine, particularly the sympatholytic effects, are suggestive of its benefits in the perioperative care of patients with cancer [ 5 , 6 ]. Further, a recent in vivo study has shown that dexmedetomidine inhibits esophageal cancer progression via miR-143-3P/epidermal growth factor receptor pathway substrate 8 [ 7 ]. However, results of in vitro and in vivo studies of dexmedetomidine revealed that tumor cell proliferation and metastasis are promoted, and overall survival is reduced [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Anesthesia Techniques and Long-Term Oncological Outcomes

“…Dexmedetomidine has also gained interest due to its sedative and analgesic effects. In esophageal carcinoma, dexmedetomidine inhibits tumor growth and metastasis via upregulation of miR-143-3p and reduction of levels of epidermal growth factor receptor 8 ( 94 ). Additionally dexmedetomidine enhances immune surveillance by inhibiting the p38 MAPK/NF-κB signaling pathway; however, some authors have indicated that dexmedetomidine can stimulate proliferation of cancer cells ( 95 , 96 ).…”

Effect of dexmedetomidine on miR-144-3p expression and epithelial mesenchymal transition in gastric cancer cells

“…Dexmedetomidine (DEX) up-regulated the expression of miR-155 in ovarian cancer cells, thereby inhibiting the tumor-promoting effect mediated by HIF-1α [9]. It has also been demonstrated that DEX promoted the expression of miR-143-3p and inhibited the malignant behavior of esophageal cancer cells [10]. These results indicate that DEX exerts different effects on different malignant tumor cells.…”