Research On The Effect And Mechanism Of Psoralen In Enhancing The Sensitivity Of Breast And Gastric Cancer Treatment

Objective: Breast cancer is the most common hormone-dependent malignant tumor in women.For estrogen receptor positive(ER+)patients,endocrine,chemotherapy and radiotherapy are often used in the patients,which can make the patients gain certain clinical benefits.Isobavachalcone(IBC)is a kind of flavonoids,which belongs to the composition of chalcone in the important psoralen.It has the biological activity of anti-tumor,anti-bacterial and anti-inflammatory.It also has the effect of estrogen-like.The purpose of this paper is to evaluate the role of IBC in ER+ breast cancer chemotherapy.Methods: MTT and flat clones were used to detect the toxicity of IBC drugs to breast cancer cells.The expression level of key genes in breast cancer cells was detected by Real-time PCR and Western blot.Flow cytometry was used to evaluate the changes of cell cycle.The synergistic effect of IBC and chemotherapeutic drugs was verified by the nude mice bearing tumor experiment.All data were analyzed by SPSS 21.0 software.Results: We have found that 17 ?-estrogen(E2)can lead to paclitaxel resistance in breast cancer cells,and IBC can reverse the drug resistance caused by E2;E2 and IBC change the resistance of ER+ cells to paclitaxel through the ER alpha pathway.Furthermore,it is confirmed that E2 and ER? can up regulate the expression level of CD44 in paclitaxel-resistant breast cancer cell our established,while IBC can inhibit the regulation of CD44 gene expression by E2.Finally,IBC down-regulated ER? and CD44 expression thereby inhibited tumor growth in paclitaxel-resistant cells xenograft tumor model.Conclusions: our data demonstrated for the first time that IBC could decrease CD44 expression level via ER? pathway and ER+ breast cancer cells resistance with paclitaxel treatment.This finding provides a theoretical basis for the treatment of ER+ breast cancer.Objective: Gastric cancer(GC)is the fourth most common malignant tumor in the world,most of which belong to adenocarcinoma,and the ratio of male and female incidence is 2:1.Estrogen receptor beta(estrogen receptor ?,ER?)is a steroid hormone receptor.Its expression level in gastric cancer is significantly higher than that of ER alpha,suggesting that ER beta plays an important role in the treatment of gastric cancer.Isobavachalcone(IBC),as a kind of phytoestrogen,can regulate the expression of ER beta.Apatinib,a novel molecular targeting agent used in the treatment of advanced gastric cancer.Hence,the present study sought to design a zebrafish model implanted the human gastric cancer cell line for studying personalized molecular-targeted cancer therapy,which was evaluated in vivo efficacy of IBC combined with apatinib in the treatment of gastric cancer.Methods: MTT assay was used to detect the toxicity of IBC drugs to gastric cancer cells.The expression level of key genes in gastric cancer cells was detected by Western blot.Then,MTT and Realtime PCR were used to evaluate the effect of apatinib on cells and the regulation of ER.The synergistic effect of IBC and apatinib was verified by the zebrafish bearing tumor experiment.All data were analyzed by SPSS 21.0 software.Results: We found that IBC could enhance the expression of ER beta and promote the apoptosis of gastric cancer cells.In the zebrafish animal model,IBC combined with apatinib exhibited the best antitumor growth effect with dose and time dependence,which may be the mechanism underlying the profound antitumor clinical effect of apatinib.Conclusions: The data indicated that IBC combined with apatinib therapy should be effective anti-angiogenesis and can be recommended as a proper antitumor growth therapy for GC patients.Moreover,zebrafish models could be designed as a potential practical tool to explore new anti-gastric cancer drugs.