Effects Of Parthenolide On The Proliferation And Apoptosis Of Small Cell Lung Cancer Cell Line NCI-H446

ObjectiveTo investigate the effects of parthenolide(PTL) on the proliferation and apoptpsis of human proliferation and apoptosis of human small cell lung cancer cell line NCI-H446 and its mechanisms.MethodsCells were divided into control group and drug treatment group(1.5μg /ml, 2.0μg /ml, 2.5μg /ml and 3.0μg /ml). NCI-H446 cells were treated with different concentrations of parthenolide, the cellular proliferative activity was determined by MTT assay. Morphologic changes were observed by fluorescence microscope. The apoptosis rates of cell were examined by flow cytometry. The expression of NF-κB, Caspase-3, Caspase-8 and Caspase-9 genes of NCI-H446 cells was detectde by RT-PCR assay. The expression of NF-κB, Caspase-3, Caspase-8 and Caspase-9 proteins of NCI-H446 cells was evaluated by Western Blot.Results1.MTT assay shouwed that Parthenolide inhibited the proliferation of NCI-H446 cells in a dose-dependent manner.2.Fluorescent microscopy showed that the number of NCI-H446 cells were reduced with Hoechst 33258 staining,the nucleus pycnosis fracture and apoptotic bodies were observed.3.Flow cytometry showed that the rate of cell apoptosis was positively correlated with the concentration of PTL, the difference was statistically significant(P< 0.05).4.Compared with control group, q RT-PCR and Western blot revealed that the expression of m RNA and protein of NF-κB in NCI-H446 cells were reduced, at the same time PTL increased the expression of Caspase 3, 8, 9, genes and proteins, and differences were statistically significant(P<0.05).ConclusionPTL could repress cellular proliferation activity and induce apoptosis of NCI-H446 cells. The mechanisms could relate to inhibition of NF-κB signaling pathway and activation of Caspases system.