In Vitro And In Vivo Potential Antitumor Effect Of Harmine In The Treatment Of Thyroid Cancer

Background:Tyroid cancer is one of the most common types of cancer in endocrine system.In latest studies,there are four main types.The differentiated thyroid carcinoma from follicular epithelium includes thyroid papillary carcinoma and follicular carcinoma,which accounts for more than 90% of thyroid cancer.Papillary thyroid carcinoma(PTC)is the most common one.Although differentiated thyroid cancer,including PTC,is low and highly reversible,the recurrence rate of these tumors is high after initial treatment.Thyroid cancer is not sensitive to conventional chemotherapy drugs,and the latter has a large side effect.Therefore,it is very important to develop new anticancer drugs.Recently,more and more evidence to prove that the promising anti-tumor traditional Chinese medicine(TCM)including harmine(HM)in recent years is regarded as a promising cancer drug candidate,however,to HM biological effect and mechanism of action of thyroid cancer are still unclear.In this preliminary study,we observe the anti-tumor effect of HM on human thyroid cancer,and further explored its possible anticancer mechanism.Objective:In the current study,we evaluated the in vitro and in vivo anticancer efficiency of harmine against thyroid cancer cell line TPC-1.Methods:The cell inhibition effect of harmine was measured by XTT assay.Apoptosis of thyroid cancer cell line TPC-1 was measured by DAPI staining.Flow cytometryinstrument further testing cell apoptosis rate;Through DNA testing and HM on the TPC-1 cell clone formation;Related apoptotic protein expression was evaluated by western blotting and Elisa.Influences of harmine on the migration and invasion of TPC-1 cells were also examined by wound scratching and Transwell assays.HM effect in vivo transplantation tumor in nude mice to observe antitumor effects in the body.Results:XTT showed that Harmine could inhibited human thyroid cancer cell line TPC-1 in a dose-dependent manner.IC50 of Harmine on TPC-1cells at 24 h,36 h and48 h was 16.57 ± 1.4,9.48 ± 1.1 and 5.51±0.7(ug/ml)respectively;Cell clone formation inhibition assay demonstrated that cell clones were decreased with increase of the concentration of Harmine Annexin V-FITC/ PI staining also showed a dose-dependent effect on late apoptotic.Western blotting assay showed that treatment of harmine dose-dependently induced the expression of Bax and degraded the existing Bcl-2,leading to a significant decrease in the ratio of Bcl-2/Bax,which demonstrated the progression of apoptosis.After treatment with different doses of human thyroid cancer cell,scratch-wound assay shows cell migration ability was lower than the control group,cell adhesion assay and Transwell invasion assay showed that the ability of adhesion and invasion descended with dose and time dependent.(P<0.05).In vivo evaluation showed that harmine effectively inhibited the growth of thyroid cancer in a dose-dependent manner in nude mice.Conclusion:Harmine inhibits the cell survival of human thyroid cancer cell TPC-1 in a dose-dependent manner.Harmine inhibits cell growth by inducing apoptotic;Harmine can inhibit the invasion ability of human colon cancer cells human thyroid cancer cells in vitro.