الملخص
Objective To study the mechanism of chemotherapy resistance caused by interleukin-6 (IL-6) in ovarian cancer cells and its related signal pathways. Methods Ovarian cancer cell lines A2780(IL-6 receptor positive, while non-IL-6-expressing and cisplatin/paclitaxel-responsive) and SKOV3 cell lines( overexpressing of IL-6 receptor and IL-6 and cisplatin/paclitaxel-resistant) were suitable models for this study. The effect of exogenous (a short period of treatment with recombination IL-6) and endogenous IL-6(by transfecting with plasmid encoding for sense IL-6 ) in A2780 cells or deleting of endogenous IL-6expression in SKOV3 cells (by transfecting with plasmid encoding for antisense IL-6) on the sensitivity to cisplatin and paclitaxel was investigated. Meanwhile, the mechanism of chemotherapy resistance caused by IL-6 in ovarian cancer cells and its related signal pathways were also analyzed. Results We found that both exogenous and endogenous IL-6 induce cisplatin and paclitaxel resistance in non-IL-6-expressing A2780 cells (the resistance multiple to cisplatin and paclitaxel was: exogenous, 6. 25 and 7.31; endogenous, 7. 13 -8. 34 and 7. 61 - 10. 70), while deleting of endogenous IL-6 expression in IL-6-overexpressing SKOV3 cells promotes its sensitivity to anticancer drugs ( the resistance multiple to cisplatin and paclitaxel was 0. 15 and 0. 10, 0. 10 and 0. 08). IL-6 significantly up-regulated the expression levels of mRNA and protein of drug resistance-associated genes, MDR1 and GST-π, and apoptosis-inhibiting genes, bcl-2, bcl-xL and XIAP in a dose-dependent manner in A2780 cells. In accordance with this finding, the mRNA and protein levels of MDR1 and GST-π enhanced in sense IL-6-transfected A2780 cells, and reduced in antisense IL-6-transfected SKOV3 cells compared with the corresponding parental and control vector-transfected cells, which had no difference. It was found that PD98059 [ mitogen-activated protein kinase-extracellular signalregulated kinase (MEK) inhibitor ] and wortmannin [ phosphatidylinositol 3-kinase (PI3K) inhibitor ]significantly antagonized IL-6-induced phosphorylation of extracellular signal-regulated kinase ( ERK ) and protein kinase B (Akt), respectively, and both of them blocked IL-6-induced cisplatin and paclitaxel resistance and the inhibitory effects of PD98059 and wortmannin were dependent on its concentration.Conclusions These data suggest that IL-6-induced chemoresistance may be associated with increase of both drug resistance-associated genes ( MDR1 and GST-π) and apoptosis-inhibiting genes ( bcl-2, bcl-xL and XIAP), and activation of MEK/ERK and PL3K/Akt. Therefore, modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for drug-resistant ovarian cancer.
الملخص
Aim To discuss the pathway of resveratrol for anti-acute myeloblastic leukemia.Methods Human acute myeloblastic leukemia cell Kasumi-1 was applied in this study.After different doses of Res treatment for different time, methyl thiazolyl tetrazolium(MTT)colorimetry was used to detect the cell proliferation.Furthermore, apoptosis and cell cycle were detected by flow cytometry.Western blot and reverse transcription polymerase chain reaction(RT-PCR)were used to detect the expression levels of Bcl-2 and Bax for mRNA and protein.The activity of signal transducers and activators of transcription 3(STAT3)was detected by immunoblotting and Luciferase reporter gene assay.On the other hand, leukemia-bearing mice models were made to investigate the live situation, survival time and the activation of STAT3 by Western blot and immunohistochemical method.Results Resveratrol could suppress the proliferation of Kasumi-1, and induce cell cycle arrest and apoptosis.At the same time, the ratios of Bcl-2/Bax and phosphor-signal transducers and activators of transcription 3(p-STAT3)were decreased significantly.In vivo, resveratrol could prolong the life span of Kasumi-1-bearing mice and attenuate the activity of STAT3 in a dose-dependent manner.Conclusions Resveratrol is a natural occurring chemotherapeutic agent present in Chinese Herbals.The regulatory effect on signaling pathways involved in STAT3 by resveratrol may be associated with its anti-leukemia effect.
الملخص
The application of test-driven methods in clinical immunology course can arouse students'interest,and give full play of their go-aheadism and creativity.Test-driven teaching methods surpasses the traditional teaching methods.