摘要
目的:通过转录组学研究,筛选出脑瘤一号方(GD-1)联合替莫唑胺(TMZ)抗胶质瘤的关键基因。方法:建立小鼠皮下移植胶质瘤异位模型,建模成功后分组给药,每隔3 d测量小鼠肿瘤体积;14 d后取材,HE染色观察肿瘤病理组织形态;通过转录组学及文献查阅预测GD-1联合TMZ抗胶质瘤的潜在机制。结果:与空白对照组比较,TMZ组和GD-1联合TMZ组裸鼠肿瘤平均体积明显减小(P<0.05);与TMZ组比较,GD-1联合TMZ组肿瘤体积缩小,但差异无统计学意义(P>0.05)。HE染色显示空白对照组胶质细胞瘤生长密度最高,细胞核最大、深染,与TMZ组比较,GD-1联合TMZ组胶质细胞瘤生长密度降低,细胞核颜色变浅,更多细胞核出现固缩、裂解等现象。通过转录组学研究得出,与TMZ组比较,GD-1联合TMZ组共有65个差异基因,其中上调基因有36个,下调基因有29个。通过GO富集分析和KEGG富集分析发现,与细胞发育过程中分化、凋亡及生物信号传递等相关的差异基因分别是SLC17A7、CACNA1D、MTCP1、RASIP1、BTBD16,其中在MAPK信号通路中CACNA1D下调,在PI3K-Akt信号中MTCP1下调,在cGMP-PKG信号通路CACNA1D下调。结论:GD-1联合TMZ治疗胶质瘤比单用西药TMZ干预效果更好,可进一步缩小肿瘤体积、降低肿瘤生长密度,其机制可能是上调抑制癌基因(SLC17A7、RASIP1、BTBD16),下调致癌基因(MTCP1、CACNA1D),进一步影响PI3K/Akt、CGMP/PKG、MAPK信号通路的活性,从而抑制胶质瘤生长。
Objective:To screen the key genes of Glioma Decoction-1(GD-1)in combination with temozolomide(TMZ)against glioma by transcriptomics study.Methods:A subcutaneous glioma heterotopic model was established in mice,and after successful modeling,the mice were grouped for administration,and the tumor volume was measured every third day.Samples were taken after 14 days,and the pathological histomorphology of tumors was observed by HE staining.The potential mechanism of GD-1 combined with TMZ against glioma was predicted by transcriptomics and literature review.Results:Compared with the control group,the average tumor volume of nude mice in the TMZ and TMZ-GD-1 groups was significantly reduced(P<0.05),and compared with the TMZ group,the tumor volume of the TMZGD-1 group was reduced,but the difference was not statistically significant(P>0.05).He staining showed the highest growth density of glioblastoma in the control group with the largest and hyperchromatic nuclei,and compared with the TMZ group,the TMZ-GD-1 group showed lower growth density of glioblastoma with lighter nuclei and more nuclei emerged pyknosis and lysis.By transcriptomics study,65differential genes were found in the GD-1 combined with TMZ group compared with the TMZ group,including 36 up-regulated genes and 29down-regulated genes.Through GO enrichment analysis and KEGG enrichment analysis,the differential genes related to differentiation,apoptosis and biological signaling transmission during cell development were SLC17A7,CACNA1D,MTCP1,RASIP1,BTBD16,among which CACNA1D was down-regulated in MAPK signaling pathway,MTCP1 was down-regulated in PI3K/Akt signaling pathway,and CACNA1D was down-regulated in the cGMP/PKG signaling pathway.Conclusion:GD-1 combined with TMZ has better effect in the treatment of glioma than the Western medicine TMZ alone,which could further reduce the tumor volume and lower tumor growth density.The mechanism may be up-regulation of inhibitory oncogenes(SLC17A7,RASIP1,BTBD16)and down-regulation of oncogenes(MTCP1,CACNA1D),which further affects the activity of PI3K/Akt,cGMP/PKG,MAPK signaling pathways,thereby inhibiting glioma growth.
作者
张敏
孙文超
费智敏
龚立
ZHANG Min;SUN Wenchao;FEI Zhimin;GONG Li(Neurosurgery Department,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,201203,Shanghai)
出处
《上海中医药大学学报》
CAS
2022年第S01期118-123,共6页
Academic Journal of Shanghai University of Traditional Chinese Medicine
基金
上海中医药大学理科预算内项目(2019LK018)
关键词
脑瘤一号方
替莫唑胺
胶质瘤
转录组测序
作用机制
Glioma Decoction 1
temozolomide
glioma
transcriptome sequencing
action mechanism
作者简介
张敏,女,硕士,主治医师,主要从事中药治疗胶质瘤的研究
