Research on JAK3/STAT3 mechanism of non-small cell lung cancer NCI-H1975 cells treated with cryptotanshinone com-bined with cisplatin / 实用肿瘤学杂志

ABSTRACT

Objective The aim of this study was to investigate the synergistic anti-tumor effect of cryptotanshinone and cis-platin 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 de-creased 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 com-bined 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.