The Effects And Mechanism Of Staurosporine On Human Thyroid Cancer SW579Cell Line In Vitro

Thyroid cancer is the most common malignant tumors of the endocrine system.Differentiated thyroid cancer(DTC), which includes papillary thyroid cancer andfollicular thyroid cancer, comprise the vast majority (90%)of all the thyroid cancers.Although, most people with DTC can achieve good prognosis with the treatment ofsurgery、radioiodine ablation and TSH suppression therapy, some patients may suffergreater local and distant recurrence rate for the early metastasis and theincompleteness of the surgery placing the recurrent laryngeal nerve and theparathyroid gland at the risk of injury, and may fail to the treatment of radioiodineablation and TSH suppression therapy, which may lead to a poor prognosis. So moreefforts are needed to sought for new therapeutic strategies for the advanced andprogressive DTC.Autophagy is an self-protective mechanism by which cells respond to stress. Instudies during the past three decades, autophagy is often observed in establishedcancers as an response to the stressors that include hypoxia and starvation. Thus,tumors perceived to use autophagy as a seif-protective mechanism. Autophagyinhibition has been shown to sensitize tumor cells to many treatment, such asirradiation and alkylating agents, suggesting that autophagy may be a partlyexplanation for cancer cells resisted to chemo-or radiation therapy. Autophagyinhibition may become a new strategy for cancer therapy.The bacterial alkaloid Staurosporine,as considered to be a protein C inhibitor, isa well-established cell death inducer through its apoptosis-inducing efficacy. Thus itcan provide an new way for cancer treatment.[Objective]: To investigate the effects and mechanism of staurosporine onhuman thyroid cancer SW579cell line in vitro.[Methods]: Cell growth inhibition of SW579induced by staurosporine wasassessed with methylthiazolyl tetrazolium(MTT) assay，cell cycle distribution was evaluated by flow cytometry and apoptosis induction was also evaluated by flowcytometry and hochest33258staining. Autophagy induction was also evaluated bymonodansylcadaverine(MDC) staining. Changes of cell cycle or apoptosis orautophagy-related proteins were evaluated by western blot analysis.[Results]： Methyl thiazolyl tetrazolium (MTT) assays indicated thatstaurosporine decreased the viability of SW579cells in a dose-and time-dependentmanner. Flow cytometry analysis indicated that staurosporine increased cellpopulation at G0-G1phase, an index of apoptosis. Furthermore,staurosporine-induced cell death was associated with apoptosis induced by theincreased release of cytochrome C. Staurosporine stimulated autophagy wasevidenced by punctuate monodansylcadaverine(MDC) staining and the increasedprotein levels of beclin1. Autophagy inhibitors3-methylademine (3-MA) sensitizedthe cytotoxicity of staurosporine.[Conclusion]： Together, these findings indicate that staurosporine inducesG0-G1phase arrest and apoptosis in SW579cells and autophagy suppressedstaurosporine-induced apoptosis. This study thus suggests that the inhibition fofautophagy can increase the cytotoxicity of staurosporine to SW579cells.