Abstract: Objective The aim of this study was to investigate the synergistic anti-tumor effect of cryptotanshinone and cisplatin in non-small cell lung cancer NCI-H1975 cells and its possible molecular mechanism.Methods NCI-H1975 cells were treated with control,cryptotanshinone,cisplatin or combination of cryptotanshinone and cisplatin groups(referred to as the combination group).The inhibitory rate of cell proliferation was determined in NCI-H1975 cells by CCK-8 assay;Flow cytometry was used to determine the rates of survival and cell apoptosis;The expression of apoptotic protein,anti-apoptotic protein,JAK2/STAT3 protein and its phosphorylation levels were detected in NCI-H1975 cells by Western blot.The localization and transcription activity of STAT3 cells were determined by laser confocal microscopy/luciferase assays.Results 1.The survival rates in cryptotanshinone,cisplatin and combination groups at each time-point were lower in NCI-H1975 cells than that in the control group(P＜0.05);The proliferation of NCI-H1975 cells in the combination group were inhibited when compared to the control,cryptotanshinone,or cisplatin groups(P＜0.05);2.After treatments for 24 h,the expression levels of Bcl-2 and Survivin protein were decreased(P＜0.01),the activity of Caspase3 and Caspase9 protein was increased(P＜0.01),and the expression levels of p-STAT3 and p-JAK2 protein were decreased in NCI-H1975 cells(P＜0.01);3.After NCI-H1975 cells treated with the combination of cryptotanshinone and cisplatin,the STAT3 in the nucleus was decreased,and STAT3 activity was also decreased in the nucleus.Conclusion Cryptotanshinone combined with cisplatin can exert a synergistic antitumor effect on non-small cell lung cancer NCI-H1975 cells,and its mechanism is related to the inhibition of JAK2 and STAT3 phosphorylation signal pathways.

Key words: Cryptotanshinone, Cisplatin, Non-small cell lung cancer, JAK2/STAT3