Department of Anesthesiology, The Second Affiliated Hospital of Mudanjiang, No. 51 Kangjia Street, Aimin District, Mudanjiang City, 157011, Heilongjiang Province, China.
Department of Ultrasound, The Second Affiliated Hospital of Mudanjiang, Mudanjiang, Heilongjiang, China.
BMC Anesthesiol. 2020 Oct 30;20(1):275. doi: 10.1186/s12871-020-01179-4.
Local anesthetic Bupivacaine commonly used in gastric cancer resection operation has been reported to suppress the progression of gastric cancer. However, the specific mechanism by which Bupivacaine functions is largely unexplored.
The viability and metastasis of gastric cancer cells were assessed by Cell counting kit-8 (CCK8) assay and transwell migration and invasion assays. The apoptosis was evaluated by caspase-3 activity detection assay and flow cytometry. The glycolysis was analyzed through detecting the extracellular acidification rate (ECAR) via Seahorse XF 96 Extracellular Flux Analyzer and the expression of glucose transporter type 1 (GLUT1) and lactic dehydrogenase A (LDHA) via Western blot assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circular RNA 0000376 (circ_0000376) and microRNA-145-5p (miR-145-5p). The interaction between circ_0000376 and miR-145-5p was predicted using Circular RNA Interactome database and validated by dual-luciferase reporter assay.
Bupivacaine restrained the viability, metastasis and glycolytic process while promoted the apoptosis of gastric cancer cells. Bupivacaine decreased the level of circ_0000376 while enhanced the abundance of miR-145-5p in gastric cancer cells. Circ_0000376 accelerated the malignant behaviors of gastric cancer cells. MiR-145-5p directly interacted with circ_0000376 in gastric cancer cells, and miR-145-5p was negatively regulated by circ_0000376. The addition of circ_0000376 or the interference of miR-145-5p partly reversed Bupivacaine-mediated influences in gastric cancer cells.
Bupivacaine exerted an anti-tumor role to suppress the progression of gastric cancer through reducing the abundance of circ_0000376 and up-regulating miR-145-5p.
局部麻醉药布比卡因常用于胃癌切除术，已被报道可抑制胃癌的进展。然而，布比卡因发挥作用的具体机制在很大程度上仍未被探索。
通过细胞计数试剂盒-8 (CCK8) 检测、Transwell 迁移和侵袭实验评估胃癌细胞的活力和转移。通过 caspase-3 活性检测和流式细胞术评估细胞凋亡。通过 Seahorse XF 96 细胞外通量分析仪检测细胞外酸化率 (ECAR) 和 Western blot 检测葡萄糖转运蛋白 1 (GLUT1) 和乳酸脱氢酶 A (LDHA) 的表达分析糖酵解。采用定量实时聚合酶链反应 (qRT-PCR) 检测环状 RNA 0000376 (circ_0000376) 和 microRNA-145-5p (miR-145-5p) 的表达。使用 Circular RNA Interactome 数据库预测 circ_0000376 和 miR-145-5p 之间的相互作用，并通过双荧光素酶报告基因实验进行验证。
布比卡因抑制胃癌细胞的活力、转移和糖酵解过程，同时促进其凋亡。布比卡因降低了胃癌细胞中环状 RNA 0000376 的水平，同时增加了 miR-145-5p 的丰度。circ_0000376 加速了胃癌细胞的恶性行为。miR-145-5p 直接与胃癌细胞中的 circ_0000376 相互作用，并且 circ_0000376 负调控 miR-145-5p。添加 circ_0000376 或干扰 miR-145-5p 部分逆转了布比卡因对胃癌细胞的影响。
布比卡因通过降低 circ_0000376 的丰度和上调 miR-145-5p 的表达发挥抗肿瘤作用，抑制胃癌的进展。
