Anticancer Activity And Drug Delivery System Study Of Celastrol

Since the 21th century,tumor has become one of the serious problems threatening human life and health.Now,the main therapies of tumor are solid tumor resection,radiotherapy and chemotherapy,and are constantly developing.The long history of the use of traditional Chinese medicine has made an important contribution to the treatment of natural medicine in anticancer.Studies suggest Celastrol is proteasome inhibitor,which can inhibit the activity of proteasome,accumulate proteasome target proteins,and induce cell apoptosis.Celastrol also exhibits excellent inhibitory effect on many kinds of tumor cells.In this paper,two kinds of hepatoma cells are used to determine the proliferative activity of celastrol in vitro and to study the effect of celastrol on intracellular proteins expression.The anticancer activity of celastrol is excellent in vitro,and the anticancer activity is dose-dependent.Furthermore,the anti-tumor effect is better than the traditional anticancer drug-cisplatin.However,celastrol exhibits high toxicity and low bioavailability,which have always been an obstacle to the clinical application.In this paper,we are expected to construct a nano drug delivery system of celastrol which maybe improve the water solubility and targeting of celastrol,in order to reduce the toxicity and improve the bioavailability of celastrol.Nanoscale particle size,large surface areas,adjustable pore,good thermal and chemical stability and pH-sensitive degradation make Zif-8 material as an effective carrier for drug delivery.Therefore,in this paper,we constructed the CE@Zif-8 drug delivery material based on the Zif-8,and characterized the material.The results in this paper mainly include:(1)Celastrol has excellent anti-proliferation effect on cells HepG2 and Bel-7402,with IC50 values of 1.038 ?M,0.631 ?M,respectively.The activity has been directly proved in clone formation assay.(2)It was detected by western blot that the expression of Bcl-2 decreased,while the expression of Bax and Caspase-3 increased when celastrol acted on cancer cells.(3)Celastrol exhibits sensitizing effect on the anti-proliferation activity of cisplatin.The IC50 of cisplatin alone on hepatoma cells was 4.021 ?M and 7.936 ?M.After adding 0.5 ?M celastrol,the IC50 of celastrol is 0.985 ?M and 3.115 ?M,respectively.(4)CE@Zif-8 drug loading system was successfully synthesized and characterized.