Effect Of Coix Seed Extract Combined With Temozolomide On Glioma

Background:glioma is the most common tumor in the nervous system,accounting for 50% of the incidence rate of brain tumors,including astrocytomas,oligodendrogliomas,ependymomas and mixed gliomas.Glioblastoma(GBM)is the most malignant tumor in astrocytoma,and the WHO grade is grade IV.The core of GBM treatment is surgery,followed by radiotherapy and adjuvant chemotherapy.At present,the main drug treatment of glioblastoma is temozolomide(TMZ),but GBM is more likely to develop resistance to TMZ than other types of gliomas,resulting in the decline of TMZ efficacy,and the median survival time of patients after treatment is not significantly prolonged.The activation of DNA repair pathway is the main mechanism of this phenomenon.It repairs TMZ induced DNA damage and prevents cells from entering apoptosis.In addition,several new mechanisms of drug resistance have been found,such as mi RNA involvement,drug efflux transporters,gap junction activity,the emergence of glioma stem cells and the up regulation of cell survival autophagy.While constantly exploring the mechanism of drug resistance,people are also constantly looking for drugs that can reverse drug resistance.Coixendide is an active extract of Coix seed.It has synergistic effect with radiotherapy and chemotherapy in the treatment of multiple tumors,and has been proved to be an effective adjuvant therapy for liver cancer,non-small cell lung cancer,pancreatic cancer,colorectal cancer and uterine sarcoma.However,whether it is effective for GBM and whether it can be used in combination with TMZ to improve the therapeutic effect of TMZ has not been studied.Objective:To explore the effect of Coixendide and Temozolomide in the treatment of glioblastoma,and to find its possible mechanism.Methods:the inhibition rates of glioblastoma cells(U251)in Coixendide group,Temozolomide group and drug combined group were measured by CCK-8,and the combination index(CI)was calculated by software calcusyn 2.0 to determine whether they have synergistic effect.Then RNA was extracted from each group,transcriptome sequencing was performed by illumina platform,and the differential gene expression of drug combined group and Temozolomide group was analyzed.The possible mechanism was found by GO enrichment analysis and KEGG enrichment analysis.Results:the combination index(CI)of Coixendide and Temozolomide was < 1,which proved that they had synergistic effect.Transcriptome sequencing analysis showed that there were 60 genes differentially expressed in the drug combined group compared with the Temozolomide group,including 27 up-regulated genes and 33 down-regulated genes.Go enrichment analysis showed that the differential genes were mainly involved in terms: response to organic cyclic compound,response to lipid,response to hormone,response to endogenous stimulus.KEGG enrichment analysis showed that the differential genes were mainly involved in cholesterol metabolism,salivary secretion,vascular smooth muscle contraction,c GMP-PKG signaling pathway,transcriptional misregularion in cancer,central carbon metabolism in cancer and so on.Conclusion:Coixendide and Temozolomide have synergistic effects in the treatment of glioblastoma at low doses.RNA-Seq results show that the drug combined group has differential expression of multiple genes in cholesterol metabolism,salivary secretion,vascular smooth muscle contraction,c GMP-PKG signaling pathway,transcriptional misregularion in cancer,central carbon metabolism in cancer,It may be the key to the synergistic effect of Coixendide on Temozolomide.