[1]胡薪蕊,吴 熙,殷玉琨,等.α-干扰素联合索拉菲尼对肝癌细胞增殖的抑制作用及其对STAT3通路的影响[J].陕西医学杂志,2024,(10):1309-1313.[doi:DOI:10.3969/j.issn.1000-7377.2024.10.003]
　HU Xinrui,WU Xi,YIN Yukun,et al.Inhibitory effect of α-interferon combined with sorafenib on proliferation of hepatocellular carcinoma cells and its effect on STAT3 pathway[J].,2024,(10):1309-1313.[doi:DOI:10.3969/j.issn.1000-7377.2024.10.003]
点击复制

α-干扰素联合索拉菲尼对肝癌细胞增殖的抑制作用及其对STAT3通路的影响
分享到：

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年10期
页码:
1309-1313
栏目:
基础研究
出版日期:
2024-10-05

文章信息/Info

Title:
Inhibitory effect of α-interferon combined with sorafenib on proliferation of hepatocellular carcinoma cells and its effect on STAT3 pathway
作者:
胡薪蕊; 吴 熙; 殷玉琨; 胡 刚; 冯 利
(中国医学科学院肿瘤医院,北京 100021)
Author(s):
HU Xinrui; WU Xi; YIN Yukun; HU Gang; FENG Li
(Cancer Hospital,Chinese Academy of Medical Sciences,Beijing 100021,China)
关键词:
α-干扰素;  索拉菲尼;  肝癌;  细胞增殖;  凋亡;  STAT3信号通路
Keywords:
Alpha-interferon;  Sorafenib;  Liver cancer;  Cell proliferation;  Apoptosis;  STAT3 signaling pathway
分类号:
R 735.7
DOI:
DOI:10.3969/j.issn.1000-7377.2024.10.003
文献标志码:
A
摘要:
目的:探讨α-干扰素(IFN-α)联合索拉菲尼对肝癌细胞增殖的抑制作用及其对转录激活因子3(STAT3)的影响。方法:选取人肝癌细胞株HepG2,分为空白对照组(未经任何处理的HL-60细胞)、IFN-α组(加入4000 U/ml IFN-α)、索拉菲尼组(加入2 μmol/L索拉菲尼)、IFN-α+索拉菲尼组(加入4000 U/ml和2 μmol/L索拉菲尼),取经药物处理后的各组细胞混悬液,继续培养24、48、72 h,采用CCK8检测HepG2细胞存活率,MTT法检测HepG2细胞增殖抑制率,行蛋白质免疫印迹(Western blot)、实时定量 PCR(qRT-PCR)测HepG2细胞中STAT3、Survivin mRNA和蛋白表达,并进行细胞形态学观察。结果:空白对照组细胞形态完整,轮廓清晰,呈梭形,贴壁状态良好,IFN-α组、索拉菲尼组部分胞浆肿胀、胞膜破裂、细胞形态、胞膜界限模糊不清,IFN-α+索拉菲尼组,细胞核缩小、染色质固缩、部分细胞碎裂、死亡。IFN-α+索拉菲尼组细胞增殖抑制率高于IFN-α组、索拉菲尼组(均P<0.05)。与空白对照组、IFN-α组、索拉菲尼组比较,IFN-α+索拉菲尼组细胞G1期细胞器增多,S、G2期细胞减少(均P<0.05)。与空白对照组比较,IFN-α组、索拉菲尼组、IFN-α+索拉菲尼组细胞中STAT3、Survivin mRNA和蛋白表达均降低,但IFN-α组和索拉菲尼组比较无统计学差异(均P<0.05),IFN-α+索拉菲尼组低于其余三组(均P<0.05)。结论:α-干扰素联合索拉菲尼可抑制HepG2细胞增殖并诱导凋亡,其机制可能是通过调节STAT3通路发挥作用。
Abstract:
Objective:To investigate the inhibitory effect of α-interferon(IFN-α)combined with sorafenib on the proliferation of hepatocellular carcinoma cell and its effect on transcriptional activator 3(STAT3).Methods:Human hepatocellular carcinoma cell line HepG2 was selected and divided into blank control group(HL-60 cells without any treatment),IFN-α group(adding 4000 U/ml IFN-α),sorafenib group(adding 2 μmol/L sorafenib),IFN-α+sorafenib group(adding 4000 U/ml and 2 μmol/L sorafenib).Cell suspension of each group after drug treatment was taken and cultured for 24,48 and 72 hours.The survival rate of HepG2 cells was detected by CCK8 and the proliferation inhibition rate of HepG2 cells was detected by MTT method.The expressions of STAT3 and Survivin mRNA and protein in HepG2 cells were measured by Western Blot and qRT-PCR,and the cell morphology was observed.Results:In the blank control group,the cells were in a complete shape,with clear outline,find-shaped,and well adherent state; in the IFN-α group and sorafenib group,part of the cytoplasm was swollen,the cell membrane was broken,and the cell morphology and membrane boundaries were blurred; in the IFN-α+sorafenib group,the nucleus was reduced,chromatin was contracted,and some cells were broken and died.The cell proliferation inhibition rate in IFN-α+sorafenib group was higher than that in IFN-α and sorafenib groups(all P<0.05).Compared with blank control group,IFN-α group and sorafenib group,cell organelles of IFN-α+sorafenib group increased in G1 phase,and cells of S and G2 phase decreased(all P<0.05).Compared with blank control group,STAT3,Survivin mRNA and protein expressions in IFN-α group,sorafenib group and IFN-α+sorafenib group were decreased(all P<0.05),but there was no significant difference between IFN-α group and sorafenib group(all P>0.05),and IFN-α+sorafenib group was lower than those of the other three groups(all P<0.05).Conclusion:α-interferon combined with sorafenib can inhibit proliferation and induce apoptosis of HepG2 cells,possibly by regulating STAT3 pathway.

参考文献/References:

[1] 曹振振,韩会会,杨文义.肝癌患者血清成纤维细胞生长因子21和富亮氨酸α2糖蛋白1表达情况及临床意义[J].陕西医学杂志,2023,52(3):305-308,312.
[2] 陈萍,马小平,蔡爽,等.过表达叉头盒F1对肝癌细胞增殖、周期和凋亡的影响及机制实验研究[J].陕西医学杂志,2023,52(9):1145-1149.
[3] WEI Q,LIU G,HUANG Z,et al.lncRNA PAARH impacts liver cancer cell proliferation by engaging miR65123p to target LASP1[J].Oncol Lett,2024,28(1):306.
[4] YANG Y,LIU C,WANG M,et al.Arenobufagin regulates the p62-Keap1-Nrf2 pathway to induce autophagy-dependent ferroptosis in HepG2 cells[J].Naunyn Schmiedebergs Arch Pharmacol,2024,397(7):4895-4909.
[5] 李杳瑶,刘华,孙铜林,等.鳖甲煎丸对肝癌大鼠黏着斑激酶/雷帕霉素靶蛋白通路的影响[J].陕西中医,2024,45(3):308-312.
[6] 张坤,朱强,庄雅峰,等.长链非编码RNA HAGLROS调控miR-26b/JAK2/STAT3通路对肝癌细胞上皮间质转化的影响[J].临床肿瘤学杂志,2022,27(4):331-338.
[7] HU J,CHEN K,HONG F,et al.METTL3 facilitates stemness properties and tumorigenicity of cancer stem cells in hepatocellular carcinoma through the SOCS3/JAK2/STAT3 signaling pathway[J].Cancer Gene Ther,2024,31(2):228-236.
[8] 康莉,李波,王晓栋,等.芪楼丸通过调控JAK/STAT信号通路对人肝癌HepG2细胞增殖与凋亡的影响[J].中成药,2023,45(2):429-434.
[9] 詹雯静,梁铭杰,刘媛,等.STAT3抑制剂及烟酰胺联合用药对肝癌HepG2细胞增殖的抑制作用及机制研究[J].天津医药,2022,50(7):686-692.
[10] 俞灵盈,王国兵,温鹏强,等.IFN-α/STAT1/STAT3信号在急性期川崎病PB/Breg细胞分化失衡机制中的作用及意义[J].海南医学,2021,32(13):1633-1637.
[11] 李潇芳,王玉琦,闫奔,等.敲低肝癌细胞STAT3抑制IFN1诱导的HepG2肝癌细胞增殖和迁移[J].细胞与分子免疫学杂志,2018,34(2):115-122.
[12] 李刚,曹志群,牛帅.原发性肝癌根治性切除术后不同时间TACE对血清肿瘤标志物及复发风险的影响[J].肝脏,2023,28(7):781-784.
[13] TAKANO Y,TAMAI N,YAMAWAKI M,et al.Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms[J].DEN Open,2024,5(1):e372.
[14] 石功亮,何勇,颜艳倩.槐耳颗粒联合分子靶向药物治疗脾虚型原发性肝癌的临床疗效[J].西部医学,2024,36(1):120-124.
[15] KHANUJA H K,AWASTHI R,DUREJA H.Sorafenib tosylate-loaded nanosuspension:Preparation,optimization,and in vitro cytotoxicity study against human HepG2 carcinoma cells[J].J Chemother,2024,36(4):299-318.
[16] 代娟,胡杰,彭胡.限制性因子黏液病毒抗性蛋白Ⅱ对乙型肝炎病毒复制的影响[J].成都医学院学报,2022,17(5):597-601.
[17] 章馨允,郭洪生,吴尘轩.肝癌免疫治疗临床进展及展望[J].中国慢性病预防与控制,2023,31(2):152-155.
[18] 孙玉侠,吴勉华,孙莎莎,等.基于蛋白组学探讨消癌解毒方通过IL-6/TNF-α/STAT3通路抑制肝癌小鼠肿瘤生长的作用机制[J].中药新药与临床药理,2023,34(11):1505-1513.
[19] 金长海,王芳,李艳红,等.双能CT扫描联合血清HMGA2和STAT3检测对早期原发性肝癌患者的诊断价值分析[J].中国CT和MRI杂志,2023,21(10):125-127
[20] 卢战辉,白阳秋,孙趁意,等.海参多糖调控JAK2/STAT3/survivin通路对肝癌细胞增殖和凋亡的影响[J].中国普外基础与临床杂志,2022,29(7):875-880.
[21] 薛刚,刘杰,许利军,等.扶正消积胶囊对胃癌细胞BGC-823的增殖抑制及凋亡的影响[J].世界中医药,2021,16(10):1526-1529,1533.
[22] 王慧,郑亚云,张隆陶,等.肝脏超声剪切波速度与肝癌病灶内血管新生及Survivin、PTEN的关系研究[J].实用癌症杂志,2022,37(5):702-705,711.
[23] SHARMA S,GHUFRAN S M,AFTAB M,et al.Survivin inhibition ameliorates liver fibrosis by inducing hepatic stellate cell senescence and depleting hepatic macrophage population[J].J Cell Commun Signal,2024,18(1):e12015.
[24] 陈亲富.有丝分裂期着丝粒粘连的分子机制研究[D].浙江:浙江大学,2020.
[25] 王成志,彭元亮,史夏青,等.葫芦素Ⅰ对肝癌细胞生长的抑制作用及其与STAT3通路相关抗凋亡因子的关系[J].中国普通外科杂志,2018,27(1):61-67.

备注/Memo

备注/Memo:
基金项目:北京市重大疑难疾病中西医协同攻关项目(2023BJSYNZDJBXTGG-004)
更新日期/Last Update: 2024-10-08