Effect and Mechanism of S-adenosylmethionine on Reversing Chemotherapy Resistance in Pancreatic Cancer
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/GEM 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 IC50 value decreased from 1557.50±201.10nmol/L to 218.39±20.61 nmol/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/GEM 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.
NETL
NSTL
万方数据
