丙泊酚通过抑制JNK/ERK1/2通路抑制鼻咽癌C666-1细胞的增殖、迁移和侵袭  

Propofol Inhibits the Proliferation,Migration and Invasion of Nasopharyngeal Carcinoma C666-1 Cells by Inhibiting the JNK/ERK1/2 Pathway

作　　者：唐思洋 肖妍芹 蒋振华 刘雨禾 毛洪波 王波 TANG Siyang;XIAO Yanqin;JIANG Zhenhua;LIU Yuhe;MAO Hongbo;WANG Bo(Department of Otolaryngology,Mianyang Central Hospital,Mianyang,Sichuan,621000,China;Department of Emergency,Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan,646000,China)

机构地区：[1]绵阳中心医院耳鼻喉科,四川省绵阳市621000 [2]西南医科大学附属医院急诊科,四川省泸州市646000

出　　处：《医学分子生物学杂志》2021年第6期444-450,共7页Journal of Medical Molecular Biology

基　　金：2019年绵阳市应用技术研究与开发项目(No.2019YFZJ022)。

摘　　要：目的探讨丙泊酚对鼻咽癌C666-1细胞的作用及机制。方法C666-1细胞分为4组:对照组、丙泊酚22、33、44μmol/L组。CCK-8实验、流式细胞术、Transwell实验分别检测细胞活力、凋亡、侵袭和迁移能力;Western印迹检测凋亡和侵袭相关蛋白表达。JNK抑制剂SP600125或ERK1/2抑制剂U0126与丙泊酚(44μmol/L)单独或联合处理细胞后,Western印迹检测JNK和ERK1/2蛋白磷酸化,CCK-8检测细胞活性。构建裸鼠移植瘤,免疫组化检测瘤组织中p-JNK、p-ERK1/2和Ki67的表达,TUNEL检测瘤组织细胞凋亡。结果与0μmol/L组比较,丙泊酚33μmol/L及以上浓度明显抑制C666-1细胞活力(P<0.05)。与对照组比较,丙泊酚33和44μmol/L组C666-1细胞中凋亡相关蛋白表达升高(P<0.05),细胞凋亡数增加(P<0.05);细胞侵袭和迁移数减少(P<0.05),侵袭相关蛋白及JNK和ERK1/2磷酸化水平显著降低(P<0.05),SP600125或U0126与丙泊酚单独或联合组均降低细胞存活率(P<0.05)。丙泊酚显著抑制移植瘤生长并促进凋亡(P<0.05)。结论丙泊酚通过抑制JNK/ERK1/2通路诱导鼻咽癌C666-1细胞凋亡,抑制增殖、侵袭和移植瘤生长。Objective To explore the effect and mechanism of propofol on nasopharyngeal carcinoma C666-1 cells.Methods C666-1 cells were divided into 4 groups:control group,propofol 22μmol/L,33μmol/L,and 44μmol/L group.CCK-8,flow cytometry and Transwell migration assay were used to detect cell viability,apoptosis,cell invasion and migration ability.Western blotting was employed to detect the expressions of apoptosis-and invasion-related proteins.After treatment with propofol(44μmol/L)and JNK inhibitor SP600125 or ERK1/2 inhibitor U0126 alone or in combination,western blotting was employed to detect the phosphorylation of JNK and ERK1/2,CCK-8 was used to detect cell viability.The xenograft tumors in nude mice were constructed.The expression levels of p-JNK,p-ERK1/2 and Ki67 in tumor tissues were detected by immunohistochemical assay,and apoptosis of tumor cells was detected by TUNEL.Results Compared with the 0μmol/Lgroup,propofol inhibited the C666-1 cell viability when it was not less than 33μmol/L(P<0.05).Compared with the control group,the expression levels of apoptosis-related proteins in C666-1 cell in the propofol 33μmol/L and 44μmol/L groups were increased,the number of apoptotic cells was increased(P<0.05).The number of cell invasion and migration was decreased(P<0.05).The levels of invasion-related proteins and phosphorylation levels of JNK and ERK1/2 were significantly decreased(P<0.05).SP600125 or U0126 alone or in combination with propofol decreased the cell survival rate(P<0.05).Propofol significantly inhibited tumor growth and promoted apoptosis(P<0.05).Conclusion Propofol induces apoptosis nasopharyngeal carcinoma C666-1 cells and inhibits proliferation,invasion and transplanted tumor growth by inhibiting JNK/ERK1/2 pathway.

关 键 词：丙泊酚 鼻咽癌 C666-1 侵袭 迁移 ERK1/2/JNK通路 

分 类 号：R739.63[医药卫生—肿瘤]