Department of Anesthesiology, Jin Yin-tan Hospital, Wuhan, Hubei, China.
Department of Surgery, Wuhan Institute for Tuberculosis Control, Wuhan, Hubei, China.
Bioengineered. 2021 Dec;12(2):11213-11224. doi: 10.1080/21655979.2021.2009318.
Cisatracurium besilate is the most commonly used non-depolarizing muscle relaxant in general anesthesia and in intensive care units. Studies have indicated that the proliferation of gastric cancer (GC) cells can be restrained by cisatracurium besilate. The present study aimed to investigate the mechanism underlying the role of cisatracurium besilate in TNF-related apoptosis-inducing ligand (TRAIL)-induced GC. The AGS cell line was exposed to cisatracurium besilate, and then cell viability, colony formation and apoptosis were assessed by performing Cell Counting Kit-8, colony formation, TUNEL and Western blot assays, respectively. Furthermore, the expression levels of p53 and p53 upregulated modulator of apoptosis (PUMA) were measured by Western blotting to determine the effect of cisatracurium besilate on p53/PUMA signaling. After co-treatment with p53 inhibitor, cisatracurium besilate and pifithrin-α/TRAIL, cell apoptosis was detected. Finally, cisatracurium besilate and pifithrin-α were used to co-treat TRAIL-induced AGS cells followed by apoptosis detection. Cisatracurium besilate treatment restrained the proliferation and promoted the apoptosis of AGS cells. Cisatracurium besilate also promoted the expression of p53 and PUMA in AGS cells. Furthermore, TRAIL induced the apoptosis of AGS cells, which was aggravated by cisatracurium besilate treatment. However, pifithrin-α reversed the synergistic effects of cisatracurium besilate and TRAIL on the activities of AGS cells. Therefore, the present study suggested that cisatracurium besilate enhanced the TRAIL-induced apoptosis of GC cells via p53 signaling, and the synergistic effects of cisatracurium besilate and TRAIL may achieve maximal therapeutic efficacy in GC management.
苯磺酸顺阿曲库铵是全身麻醉和重症监护病房中最常用的非去极化肌松药。研究表明，苯磺酸顺阿曲库铵可以抑制胃癌（GC）细胞的增殖。本研究旨在探讨苯磺酸顺阿曲库铵在 TNF 相关凋亡诱导配体（TRAIL）诱导 GC 中的作用机制。AGS 细胞系暴露于苯磺酸顺阿曲库铵中，然后通过细胞计数试剂盒-8 法、集落形成实验、TUNEL 法和 Western blot 法分别评估细胞活力、集落形成和细胞凋亡。此外，通过 Western blot 法测定 p53 和 p53 上调凋亡调节剂（PUMA）的表达水平，以确定苯磺酸顺阿曲库铵对 p53/PUMA 信号通路的影响。用 p53 抑制剂共处理后，检测苯磺酸顺阿曲库铵和 pifithrin-α/TRAIL 对细胞凋亡的影响。最后，用苯磺酸顺阿曲库铵和 pifithrin-α共同处理 TRAIL 诱导的 AGS 细胞，然后检测细胞凋亡。苯磺酸顺阿曲库铵处理可抑制 AGS 细胞的增殖并促进其凋亡。苯磺酸顺阿曲库铵还可促进 AGS 细胞中 p53 和 PUMA 的表达。此外，TRAIL 诱导 AGS 细胞凋亡，而苯磺酸顺阿曲库铵处理则加重了这种凋亡。然而，pifithrin-α 逆转了苯磺酸顺阿曲库铵和 TRAIL 对 AGS 细胞活性的协同作用。因此，本研究表明，苯磺酸顺阿曲库铵通过 p53 信号增强了 TRAIL 诱导的 GC 细胞凋亡，而苯磺酸顺阿曲库铵和 TRAIL 的协同作用可能在 GC 管理中达到最大的治疗效果。
