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目的:研究冷冻消融术对肺腺癌小鼠MAPK/ERK信号通路的调节作用。方法:采用Lewis小鼠肺腺癌细胞株建立C57BL/6小鼠皮下移植瘤模型,选取造模成功的10只小鼠随机分成2组,假手术组和冷冻消融组,每组5只,冷冻消融组小鼠选用双循环冷冻消融术,假手术组于移植瘤处切开缝合,术后14 d取肿瘤组织,通过Western blot检测冷冻消融对MAPK/ERK通路相关蛋白KRAS、RAF1、MEK1、ERK1/2、P-RAF1、P-MEK1、P-ERK1/2的影响,采用qRt-PCR进一步验证通路关键分子KRas基因表达情况。结果:与假手术组比,冷冻消融术后肿瘤组织中磷酸化蛋白P-RAF1、P-MEK1、P-ERK1/2降低(P<0.05),MAPK/ERK通路关键分子KRAS在蛋白和基因表达上均降低(P<0.05)。结论:冷冻消融可以通过下调KRAS表达,负向调控MAPK/ERK信号通路。
Abstract:Objective:To study the regulatory effect of cryoablation on MAPK/ERK signaling pathway in mice with lung adenocarcinoma. Methods:Lewis mouse lung adenocarcinoma cell line was used to establish subcutaneous transplanted tumor model in C57BL/6 mice. Ten mice were randomly divided into two groups:sham operation group and cryoablation group,with 5mice in each group. The cryoablation group was treated with double circulation-rewarming ablation,and the sham operation group was treated with incision and suture at the transplanted tumor. The tumor tissues were taken 14 days after operation. Detect the effect of cryoablation on MAPK/ERK pathway related proteins by Western blot,such as KRAS,RAF1,MEK1,ERK1/2,P-RAF1,P-MEK1 and P-ERK1/2. The expression of KRas gene was further verified by qRt-PCR. Results:Compared with the sham operation group,the phosphorylated proteins P-RAF1,P-MEK1 and P-ERK1/2 in tumor tissue after cryoablation were decreased(P<0.05),and the key molecule KRAS in MAPK/ERK pathway was decreased in protein and gene expression(P<0.05). Conclusion:Cryoablation can negatively regulate MAPK/ERK signaling pathway by down-regulating KRas expression.
1 Sung H,Ferlay J,Siegel RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CACancer J Clin,2021,71(3):209-249.
2 Hanahan D,Weinberg RA.Hallmarks of Cancer:the Next Generation[J].Cell,2011,144(5):646-674.
3 Zhang K,Ding J.In vitro anticancer effects of levopimaric acid in cisplatin-resistant human lung carcinoma are mediated via autophagy,ROS-mediated mitochondrial dysfunction,cell apoptosis and modulation of ERK/MAPK/JNK signalling pathway[J].J BUON,2020,25(1):248-254.
4 Wu Q,Liu TY,Hu BC,et al.CK-3,A novel methsulfonyl pyridine derivative,suppresses hepatocellular carcinoma proliferation and invasion by blocking the PI3K/AKT/m TOR and MAPK/ERK pathways[J].Front Oncol,2021,11:717626.
5 Yang CY,Wang J,Zhang JQ,et al.Human circular RNAhsa_circ RNA_101705 (circ TXNDC11) regulates renal cancer progression by regulating MAPK/ERK pathway[J].Bioengineered,2021,12(1):4432-4441.
6 Cao W,Chen HD,Yu YW,et al.Changing profiles of cancer burden worldwide and in China:a secondary analysis of the global cancer statistics 2020[J].Chin Med J(Engl),2021,134(7):783-791.
7翟焕阁,肖正红,杨双林.CT引导下氩氦刀冷冻消融术辅助治疗原发性肝癌对肿瘤组织血流变化的影响[J].中国CT和MRI杂志,2021,19(9):96-99,110.
8 Yi F,Liu L,Ding M,et al.Changes in and effects of Kupffer cells on residual tumor after cryoablation in rabbit hepatic VX2 tumor[J].Int J Clin Exp Pathol,2021,14(1):75-85.
9 Urano M,Tanaka C,Sugiyama Y,et al.Antitumor effects of residual tumor after cryoablation:the combined effect of residual tumor and a protein-bound polysaccharide on multiple liver metastases in a murine model[J].Cryobiology,2003,46(3):238-245.
10 Veenstra JJ,Gibson HM,Littrup PJ,et al.Cryotherapy with concurrent Cp G oligonucleotide treatment controls local tumor recurrence and modulates HER2/neu immunity[J].Cancer Res,2014,74(19):5409-5420.
11 Lundin A,Driscoll B.Lung cancer stem cells:Progress and prospects[J].Cancer Lett,2013,338(1):89-93.
12 Suh JH,Johnson A,Albacker L,et al.Comprehensive genomic profiling facilitates implementation of the national comprehensive cancer network guidelines for lung cancer biomarker testing and identifies patients who may benefit from enrollment in mechanism-driven clinical trials[J].Oncologist,2016,21(6):684-691.
基本信息:
DOI:10.13210/j.cnki.jhmu.20211119.001
中图分类号:R734.2
引用信息:
[1]林事成,刘殿娜,周相男,等.基于MAPK/ERK信号通路探讨冷冻消融对肺癌小鼠的作用机制[J].海南医学院学报,2022,28(06):420-424.DOI:10.13210/j.cnki.jhmu.20211119.001.
基金信息:
北京中医药大学重点攻关项目(2020-JYB-ZDGG-127); 国家重点研发计划资助项目(2018YFC1705102)~~
2021-11-22
2021-11-22
2021-11-22