S-腺苷甲硫氨酸逆转胰腺癌化疗耐药的作用及机制研究  

Effect and Mechanism of s-adenosylmethionine on Reversing Chemotherapy Resistance in Pancreatic Cancer

作　　者：刘岩 丁子明 张前进[1] 赵军抗 满忠松 李永[1] LIU Yan;DING Ziming;ZHANG Qianjin(Department of General Surgery,Xuzhou Central Hospital,Xuzhou Clinical School of Xuzhou Medical University,Jiangsu 221006,China)

机构地区：[1]徐州市中心医院、徐州医科大学徐州临床学院,221006

出　　处：《医学研究杂志》2024年第7期146-151,共6页Journal of Medical Research

基　　金：徐州医科大学附属医院优秀人才基金资助项目(XYFY202201)。

摘　　要：目的研究S-腺苷甲硫氨酸(S-adenosylmethionine,SAM)对胰腺癌化疗耐药的逆转作用并探讨相关机制。方法SAM处理人胰腺癌耐药细胞株PANC-1/GEM后,MTT实验研究细胞增殖活性的变化以及对吉西他滨(gemcitabine,GEM)化疗耐药性的影响;流式细胞术探讨SAM对胰腺癌耐药细胞株凋亡率的影响;细胞划痕实验分析SAM对耐药细胞株迁移活性能力的改变;Western blot法检测耐药株中NEDD4-1蛋白的表达变化及SAM处理后细胞内NEDD4-1、p-JAK2、p-STAT3及P-gp蛋白水平的变化。结果SAM作用于胰腺癌PANC-1/GEM耐药细胞株后,可抑制细胞株的生长活力并可明显降低其对GEM化疗的耐药活性,IC50值由1557.50±201.10nmol/L降低至218.39±20.61nmol/L(P<0.01);SAM明显诱导耐药细胞株发生凋亡且可抑制其迁移的活性;耐药细胞株中NEDD4-1蛋白表达上调,且SAM可抑制耐药株中NEDD4-1、p-JAK2、p-STAT3及P-gp蛋白的活化水平。结论SAM可通过调控NEDD4-1抑制JAK2/STAT3通路活性并调控P-gp蛋白的活性降低PANC-1/GEM细胞对GEM的化疗耐药性,为后续SAM应用于临床治疗肿瘤患者的化疗耐药提供一定的实验依据。Objective To studyexplore the reversal effect of S-adenosylmethionine(SAM)on chemotherapy resistancechemoresis-tance of pancreatic cancer and explore its related mechanisms.Methods After treatment of human pancreatic cancer resistant cell lines PANC-1/GEM with SAM,the cell proliferation activity of PANC-1/GEM cells and their resistance to gemcitabine(GEM)were ana-lyzed by MTT assay;The the effect of SAM on apoptosis rate of PANC-1/CEM cells was detected by flow cytometry;the change of SAM on the migration activity of drug-resistant cell lines was detected by cell scratch assay;the expression of NEDD4-1 protein in drug-re-sistant cell lines and the changes of NEDD4-1,p-JAK2,p-STAT3 and P-gp protein levels after SAM treatment were detected by Western blot.Results SAM could inhibit the activity of pancreatic cancer PANC-1/GEM resistant cell lines and significantly decreased its resistance to GEM chemotherapy.The ICso value decreased from 1557.50±201.10nmol/L to 218.39±20.61nmol/L(P<0.01);SAM can obviously induced the apoptosis of drug-resistant cell lines and inhibited their migration activity;the expression of NEDD4-1 protein was up-regulated in drug-resistant cell lines,and SAM could inhibit the activation levels of NEDD4-1,p-JAK2,P-STAT3 and P-gP proteins.Conclusion SAM can reduce the chemotherapy resistance of PANC-1/CEM cells to GEM by regulating NEDD4-1 to inhibit the activity of JAK2/STAT3 pathway and regulate the activity of P-gp protein,which provides some experimental evidence for the clinical application of SAM in the treatment of chemotherapy resistance in tumor patients.

关 键 词：胰腺癌 S-腺苷甲硫氨酸 吉西他滨 化疗耐药 

分 类 号：R735[医药卫生—肿瘤]