摘要
目的探讨苍术素(ATR)对非小细胞肺癌(NSCLC)HCC827细胞上皮间质转化(EMT)的影响及其机制。方法使用10.0、20.0、40.0、80.0、160.0μmol/L的ATR分别处理HCC827细胞,检测细胞存活率并确定最佳给药浓度。HCC827分为对照组、药物低(10.0μmol/L)、中(20.0μmol/L)、高(40.0μmol/L)浓度组(ATR-L组、ATR-M组、ATR-H组)、ATR(40.0μmol/L)+信号转导子与转录激活子(STAT)3激活剂(Colivelin,0.5μmol/L)组(ATR+Colivelin组)。CCK-8法检测各组细胞存活率,划痕实验检测各组细胞迁移能力,Transwell小室实验检测各组细胞侵袭能力,Western blot法检测各组细胞上皮型钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、锌指蛋白转录因子(Snail)1及Janus激酶(JAK)2/STAT3通路蛋白相对表达水平,并进行分析和比较。结果不同浓度的ATR均可显著降低HCC827细胞存活率。与对照组比较,ATR-L组、ATR-M组、ATR-H组细胞划痕愈合率与侵袭细胞数显著降低,N-cadherin、Snail1、磷酸化JAK2(p-JAK2)、磷酸化STAT3(p-STAT3)蛋白相对表达水平显著降低,E-cadherin相对表达水平显著升高,差异均有统计学意义(均P<0.05),且呈药物浓度依赖性(P<0.05);与ATR-H组比较,ATR+Colivelin组细胞划痕愈合率与侵袭细胞数显著升高,N-cadherin、Snail1、p-JAK2、pSTAT3蛋白相对表达水平显著升高,E-cadherin相对表达水平显著降低,差异均有统计学意义(均P<0.05)。结论ATR通过抑制JAK2/STAT3通路抑制HCC827细胞增殖、迁移与EMT。
Objective To investigate the effects of atractylodin(ATR)on epithelial mesenchymal transformation(EMT)and gefitinib resistance in non-small-cell lung cancer(NSCLC)HCC827 cells and its mechanism.Methods HCC827 cells were treated with 10.0,20.0,40.0,80.0,160.0μmol/L ATR,and the optimal concentration was determined by detecting cell proliferation.Then HCC827 cells were divided into control group,low(10.0μmol/L),medium(20.0μmol/L)and high(40.0μmol/L)concentration ATR(ATR-L,ATR-M,ATR-H)groups,and ATR(40.0μmol/L)+signal transducer and activator of transcription(STAT)3 activator(Colivelin,0.5μmol/L)group(ATR+Colivelin),respectively.Cell proliferation activity was detected by CCK 8 method;the cell migration and invasion ability was detected by scratch test and Transwell assay;the expression levels of epithelial cadherin(E-cadherin),N-cadherin,zinc finger protein transcription factor 1(Snail1),Janus kinase(JAK)2/STAT3 pathways were detected by Western blot assay.Results Compared with the control group,the scratch healing rate and invasive cell count in the ATR-L,ATR-M,and ATR-H groups were significantly reduced,the expression levels of N cadherin,Snail1,phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)proteins were significantly downregulated(all P<0.05),while the expression levels of E-cadherin were significantly upregulated in a concentration dependent manner(P<0.05).Compared with ATR-H group,the scratch healing rate and the number of invasive cells in ATR+Colivelin group were significantly increased,the protein expression levels of N-cadherin,Snail1,p JAK2 and p-STAT3 were significantly upregulated(all P<0.05),and the expression level of E-cadherin was significantly downregulated(P<0.05).Conclusion ATR can inhibit the proliferation,migration and EMT of NSCLC HCC827 cells by inhibiting JAK2/STAT3 pathway.
作者
朱亚兰
吕世文
曾晨欣
徐媛青
ZHU Yalan;LYU Shiwen;ZENG Chenxin;XU Yuanqing(Department of Pharmacy,Jinhua Municipal Central Hospital,Jinhua 321000,China)
出处
《浙江医学》
CAS
2023年第10期1013-1018,共6页
Zhejiang Medical Journal
基金
浙江省医学会临床科研基金资助项目(2020ZYC-B43)。
关键词
苍术素
非小细胞肺癌
Janus激酶2/信号转导子与转录激活子3信号通路
上皮间质转化
Atractylodin
Non-small-cell lung cancer
Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway
Epithelial mesenchymal transformation
