Effect Of AS1411 Triptolide Conjugate On Expression Of Apoptosis-related Genes

Targeted therapy of cancer is an emerging hotspot after the 1990 s,which has more specificity and fewer side effects than traditional radiotherapy and chemotherapy.Antibody-drug conjugates(ADCs)have the advantages of excellent specificity,better efficacy,and lower side effects on tumors,and the FDA has approved the selling of ADCs.However,the synthesis and purification of ADCs lead to the hardest barrier for further development.The complexity of the producing process and purification process result in an expensive price.Aptamers are similar to antibodies,their 3-dimensional structure empowers them to attach the specific molecule.Additionally,Aptamers are easy to be synthesized and modified,make industrial large-scale production realizable.To date,aptamers have been used in bioimaging,drug delivery,disease diagnosis,etc.Aptamer Drug Conjugates(ApDCs),as a drug delivery system better than ADCs,is a great candidate for targeted cancer therapy because of the excellent properties of aptamers.Triptolide(TPL)is a small molecule anti-tumor drug extracted from tripterygium wilfordii.TPL can exert its anti-tumor effect through tumor cell apoptosis signaling pathway,autophagy signaling pathway,tumor migration protein,and so on.This paper mainly studies the effect of AS1411-triptolide conjugate(ATC)and TPL on the apoptosis signaling pathway of triple-negative breast cancer cell MDA-MB-231 cells.The results show that both TPL and ApDC can promote the high expression of P53,Caspase3,Bcl2 and Bax genes in MDA-MB-231 cells.However,TPL has a faster action speed,stronger intensity,and shorter functional time;ApDC has a longer functional time.TPL and ApDC had the most obvious promotion effect on the expression of the Caspase3 gene.After the drug treatment,the expression of Caspase3 increased by dozens of times.Therefore,TPL and ApDC can induce apoptosis in MDA-MB-231 cells through a Caspase-dependent apoptosis signaling pathway.P53 protein is a key protein in this apoptosis pathway,and Bax protein also has a certain correlation with this apoptosis pathway.