Parthenolide Suppresses TPC-1 Human Thyroid Cancer Cells Proliferation,Migration And Invasion Via Inhibition Of The TGF-β/smad Signaling Pathway

Objective:Thyroid carcinoma is the most common endocrine malignant tumor,and its incidence is increasing all over the world.Most of the patients with differentiated thyroid cancer have a good prognosis after standard surgical treatment,¹³¹I treatment and TSH inhibition therapy.However,14.9%of the patients had persistent or recurrent disease,and 7%～23%of the patients had distant metastasis.It is a complex,multi-step,multi-gene regulation process,which involves the interaction among tumor cells,body and target tissues,as well as the regulation and signal transduction of related genes in the invasion and migration of thyroid cancer.It is the main cause of death in patients with thyroid cancer.Epithelial-mesenchymal transformation plays an important role in the metastasis of thyroid cancer.Therefore,it is necessary to find more drugs with clinical value to improve the quality of life of patients.Traditional Chinese medicine has great potential in the treatment of malignant tumors,and there are more and more researches in recent years.Parthenolide is a sesquiterpene lactone extracted from herbal plant Tanacetum parthenium.It is often used in the treatment of migraine,fever,rheumatoid arthritis and so on.More and more studies have confirmed that PTL has strong anti-tumor activity against a variety of tumors.Therefore,our study aims to explore the effects of PTL on the proliferation,migration and invasion of thyroid cancer cells and its possible mechanism.Research methods:TPC-1 cells were treated with different concentrations of PTL（0,2.5,5,10,and 20μM）for 24h,and the effect of PTL on the proliferation was detected by the CCK-8 assay.Cell cycle was analyzed by flow cytometry.We then examined the effect of PTL on cell migration and invasion via scratch and transwell assays,respectively.The protein expression of E-cadherin,N-cadherin,Vimentin,MMP-9,TGF-β,Smad3 and p-Smad3 were detected by western blotting.Results:PTL could significantly inhibit the proliferation of TPC-1 cells in a concentration-dependent manner,after TPC-1 cells were treated with different concentrations of PTL for 24 hours.With the increase of PTL concentration,more and more cells were blocked in G0/G1 phase,while S phase cells decreased gradually,and there was no significant change in G2 phase.Scratch and Transwell experiments showed that PTL could weaken the migration and invasion ability of TPC-1 cells.Western blotting results showed that PTL could up-regulate the expression of E-cadherin and down-regulate the expression of N-cadherin,Vimentin,MMP-9,TGF-βand p-Smad3.Conclusion:PTL inhibited the proliferation of thyroid cancer TPC-1 cells in a concentration-dependent manner,which may be related to G0/G1 cell cycle arrest.PTL may inhibit the invasion and migration of TPC-1 cells by regulating TGF-β/smad signal pathway and inhibiting the occurrence of EMT.PTL suppresses TPC-1 human thyroid cancer cells proliferation,migration and invasion via inhibition of the TGF-β/smad signal pathway,which may be a potential drug for clinical treatment of thyroid cancer.