蠲瘤散结方抑制肺腺癌A549细胞移植瘤的增殖及可能作用机制的探讨
发布时间：2021-07-05 09:31
目的:探讨中药蠲瘤散结方对荷人肺腺癌小鼠皮下移植瘤生长的影响及可能的作用机制。方法:体外培养人肺腺癌A549细胞,采用皮下接种的方法构建裸小鼠A549细胞移植瘤模型。实验分3组:对照组（0.9%的氯化钠溶液）、顺铂（阳性对照组）和蠲瘤散结方组,通过比较移植瘤体积和质量等指标观察蠲瘤散结方对肿瘤生长的影响。随后,采用表达谱基因芯片技术检测对照组和蠲瘤散结方组中各3个肿瘤样本基因的表达水平,筛选差异表达的基因并进行功能分析。结果:与对照组相比,顺铂组和蠲瘤散结方组移植瘤的质量和体积均明显降低,差异有统计学意义（P值均<0.05）;蠲瘤散结方组移植瘤的质量和体积略高于顺铂组,但二组间差异无统计学意义（P>0.05）。蠲瘤散结方组小鼠的体质量与对照组相比差异无统计学意义（P>0.05）,蠲瘤散结方组和对照组小鼠的体质量都明显高于顺铂组（P值均<0.05）。采用表达谱基因芯片技术检测对照组和蠲瘤散结方组移植瘤中RNA的表达情况,共筛选获得261个差异表达的基因,其中85个基因表达上调,176个基因表达下调。对差异表达基因的分析显示,蠲瘤散结方调控的差异基因多与代谢相关,如...
【文章来源】：肿瘤. 2020,40(06)北大核心CSCD
【文章页数】：9 页
【部分图文】：
采用差异表达基因聚类图(A)和火山图(B)分析蠲瘤散结方处理前后差异表达的基因
利用KEGG数据库对差异基因进行Pathway分析,并且用统计检验的方法计算每个Pathway条目中差异基因富集的显著性。整体差异基因的Pathway结果见图4A,上调基因的Pathway结果见图4B,下调基因的Pathway结果见图4C。结果显示,蠲瘤散结方调控的基因表达多与代谢相关,如卵巢类固醇生成通路、糖脂代谢通路和视黄醇代谢通路等(表3)。这也与中医药治疗肿瘤理论相应证,提示应从代谢的角度去分析中医药抑制肿瘤增殖和侵袭的具体机制。图2 采用差异表达基因聚类图(A)和火山图(B)分析蠲瘤散结方处理前后差异表达的基因
表1 蠲瘤散结方处理后差异表达倍数变化最显著的20个基因Table1 Fold change (FC) of top 20 differential expression genes after treatment of Juan Liu San Jie Formula Gene Control JLSJF Up-regulated NT5DC4 1 3.86 TMEM255B 1 3.65 SPRR2A 1 3.02 WNT2B 1 3.02 PROB1 1 2.77 DKK4 1 2.74 NUPR1 1 2.72 SPRR2E 1 2.44 CYP2B6 1 2.31 TNFSF8 1 2.30 Down-regulated PLPP7 1 6.99 CAGE1 1 5.09 HSD17B7 1 4.95 TMEM106A 1 4.76 PDE7A 1 4.61 TCEA2 1 4.61 SLMAP 1 4.51 CDH17 1 4.29 PLGLB1 1 4.03 WDR90 1 3.93NT5DC4:5’-Nucleotidase domain containing 4;TMEM255B:Transmembrane protein 255B;SPRR2A:Small proline rich protein 2A;WNT2B:Wnt family member 2B;PROB1:Proline rich basic protein 1;DKK4:Dickkopf WNT signaling pathway inhibitor 4;NUPR1:Nuclear protein 1,transcriptional regulator;SPRR2E:Small proline rich protein 2E;CYP2B6:Cytochrome P450 family 2 subfamily B member 6;TNFSF 8:TNF superfamily member 8;PLPP 7:Phospholipid phosphatase 7;CAGE 1:Cancer antigen 1;HSD 17B 7:Hydroxysteroid 17-beta dehydrogenase 7;TMEM 106A:Transmembrane protein 106A;PDE 7A:Phosphodiesterase 7A;TCEA 2:Transcription elongation factor A2;SLMAP:Sarcolemma associated protein;CDH17:Cadherin 17;PLGLB1:Plasminogen like B1;WDR90:WD repeat domain 90.Control:The mice-bearing xenograft were treated with 0.9%sodium chloride solution;JLSJF:The mice-bearing xenograft were treated with Juan Liu Jie Formula.表2 蠲瘤散结方处理后差异基因功能的GO分析Table 2 Gene Ontology (GO)-analysis of differential expression genes after treatment of Juan Liu San Jie Formula (JLSJF) GO function Gene P value Biological process (BP) Ossification involved in bone maturation PLXNB1, THBS3 0.001 238 Epoxygenase P450 pathway CYP2B6, CYP2C18 0.006 890 Exogenous drug catabolic process CYP2B6, CYP2C18 0.008 237 Glucose import HNF1A, SLC2A11 0.008 237 Cellular component (CC) Microvillus membrane PROM2, DPEP1 0.005 227 Extracellular space TNFSF8, WNT2B, ARSG, DPEP1 0.005 301 Cornified envelope SPRR2A, SPRR2E 0.008 967 Molecular function (MF) Nitric-oxide synthase binding CAMK2D, CDH2 0.004 291 Arachidonic acid epoxygenase activity CYP2B6, CYP2C18 0.005 428 Oxidoreductase activity, CYP2B6, CYP2C18 0.008 064 Cytokine receptor activity IFNLR1, IL15RA 0.008 797 Steroid hydroxylase activity CYP2B6, CYP2C18 0.009 558PLXNB 1:Plexin B1;THBS 3:Thrombospondin 3;CYP 2B 6:Cytochrome P450 family 2 subfamily B member 6;CYP 2C 18:Cytochrome P450 family 2 subfamily C member 18;HNF 1A:HNF1 homeobox A;SLC 2A 11:Solute carrier family 2 member 11;PROM 2:Prominin 2;DPEP 1:Dipeptidase 1;TNFSF 8:TNF superfamily member 8;WNT 2B:Wnt family member 2B;ARSG:Arylsulfatase G;SPRR 2A:Small proline rich protein 2A;SPRR 2E:Small proline rich protein 2E;CAMK 2D:Calcium/calmodulin dependent protein kinaseⅡdelta;CDH 2:Cadherin 2;IFNLR 1:Interferon lambda receptor 1;IL 15RA:Interleukin 15 receptor subunit alpha.
【参考文献】：
期刊论文
[1]解毒散结方醇提物抗裸小鼠人肺癌术后转移作用的研究[J]. 郑婷婷,付艳丽,焦丽静,许玲. 中药新药与临床药理. 2016(06)
[2]解毒三根汤调节肿瘤相关成纤维细胞抗结肠癌侵袭转移及其对α-SMA、Sirt1、Ki67的影响[J]. 阮善明,孙钰,张恺,孙磊涛,沈敏鹤. 浙江中医药大学学报. 2016(03)
[3]肿瘤微环境的脾虚本质探讨[J]. 韩钦芮,符秀琼,禹志领,孙学刚. 中医杂志. 2014(04)
[4]5种不同治法中药对人肺癌A549细胞增殖的影响[J]. 周燕萍,杨航,关江峰,周良发,覃双来,徐坚,胡作为. 成都中医药大学学报. 2013(03)
[5]中西医两种方法评价肺瘤平膏联合化疗治疗中晚期非小细胞肺癌疗效[J]. 张培彤,林洪生,于明薇,杨宗艳,董海涛,张培宇,贺用和. 中医杂志. 2012(05)
[6]清热解毒法对小鼠Lewis肺癌瘤组织MMP-9及TIMP-1表达的影响[J]. 高静东,陈嘉璐,张蕾,刘敏,景天驰,李湧健. 江苏中医药. 2010(10)
[7]利用数据挖掘方法对肺癌中医药治疗特点的初步研究[J]. 刘杰,林洪生,侯炜,李道睿,周雪忠. 世界科学技术(中医药现代化). 2009(05)
[8]晚期肺癌中医辨证规律探讨[J]. 张学哲,张宁苏. 实用中医内科杂志. 2008(06)
[9]苦参注射液防治肺癌化疗毒副反应的临床观察[J]. 陶玉坚. 实用临床医药杂志. 2007(05)
硕士论文
[1]基于药对的不同治法对Lewis肺癌干预效应的比较研究[D]. 丁世宏.成都中医药大学 2018
[2]清热化痰散结方及其拆方抑制人肺癌细胞SK-MES和NCI-H69 PI3K-Akt-mTOR信号转导的研究[D]. 李萌萌.河南中医药大学 2016
[3]四组常用抗癌中药配伍抗lewis肺癌作用及其机制的比较研究[D]. 陈慧彬.中国人民解放军医学院 2014
本文编号：3265820
【文章来源】：肿瘤. 2020,40(06)北大核心CSCD
【文章页数】：9 页
【部分图文】：
采用差异表达基因聚类图(A)和火山图(B)分析蠲瘤散结方处理前后差异表达的基因
利用KEGG数据库对差异基因进行Pathway分析,并且用统计检验的方法计算每个Pathway条目中差异基因富集的显著性。整体差异基因的Pathway结果见图4A,上调基因的Pathway结果见图4B,下调基因的Pathway结果见图4C。结果显示,蠲瘤散结方调控的基因表达多与代谢相关,如卵巢类固醇生成通路、糖脂代谢通路和视黄醇代谢通路等(表3)。这也与中医药治疗肿瘤理论相应证,提示应从代谢的角度去分析中医药抑制肿瘤增殖和侵袭的具体机制。图2 采用差异表达基因聚类图(A)和火山图(B)分析蠲瘤散结方处理前后差异表达的基因
表1 蠲瘤散结方处理后差异表达倍数变化最显著的20个基因Table1 Fold change (FC) of top 20 differential expression genes after treatment of Juan Liu San Jie Formula Gene Control JLSJF Up-regulated NT5DC4 1 3.86 TMEM255B 1 3.65 SPRR2A 1 3.02 WNT2B 1 3.02 PROB1 1 2.77 DKK4 1 2.74 NUPR1 1 2.72 SPRR2E 1 2.44 CYP2B6 1 2.31 TNFSF8 1 2.30 Down-regulated PLPP7 1 6.99 CAGE1 1 5.09 HSD17B7 1 4.95 TMEM106A 1 4.76 PDE7A 1 4.61 TCEA2 1 4.61 SLMAP 1 4.51 CDH17 1 4.29 PLGLB1 1 4.03 WDR90 1 3.93NT5DC4:5’-Nucleotidase domain containing 4;TMEM255B:Transmembrane protein 255B;SPRR2A:Small proline rich protein 2A;WNT2B:Wnt family member 2B;PROB1:Proline rich basic protein 1;DKK4:Dickkopf WNT signaling pathway inhibitor 4;NUPR1:Nuclear protein 1,transcriptional regulator;SPRR2E:Small proline rich protein 2E;CYP2B6:Cytochrome P450 family 2 subfamily B member 6;TNFSF 8:TNF superfamily member 8;PLPP 7:Phospholipid phosphatase 7;CAGE 1:Cancer antigen 1;HSD 17B 7:Hydroxysteroid 17-beta dehydrogenase 7;TMEM 106A:Transmembrane protein 106A;PDE 7A:Phosphodiesterase 7A;TCEA 2:Transcription elongation factor A2;SLMAP:Sarcolemma associated protein;CDH17:Cadherin 17;PLGLB1:Plasminogen like B1;WDR90:WD repeat domain 90.Control:The mice-bearing xenograft were treated with 0.9%sodium chloride solution;JLSJF:The mice-bearing xenograft were treated with Juan Liu Jie Formula.表2 蠲瘤散结方处理后差异基因功能的GO分析Table 2 Gene Ontology (GO)-analysis of differential expression genes after treatment of Juan Liu San Jie Formula (JLSJF) GO function Gene P value Biological process (BP) Ossification involved in bone maturation PLXNB1, THBS3 0.001 238 Epoxygenase P450 pathway CYP2B6, CYP2C18 0.006 890 Exogenous drug catabolic process CYP2B6, CYP2C18 0.008 237 Glucose import HNF1A, SLC2A11 0.008 237 Cellular component (CC) Microvillus membrane PROM2, DPEP1 0.005 227 Extracellular space TNFSF8, WNT2B, ARSG, DPEP1 0.005 301 Cornified envelope SPRR2A, SPRR2E 0.008 967 Molecular function (MF) Nitric-oxide synthase binding CAMK2D, CDH2 0.004 291 Arachidonic acid epoxygenase activity CYP2B6, CYP2C18 0.005 428 Oxidoreductase activity, CYP2B6, CYP2C18 0.008 064 Cytokine receptor activity IFNLR1, IL15RA 0.008 797 Steroid hydroxylase activity CYP2B6, CYP2C18 0.009 558PLXNB 1:Plexin B1;THBS 3:Thrombospondin 3;CYP 2B 6:Cytochrome P450 family 2 subfamily B member 6;CYP 2C 18:Cytochrome P450 family 2 subfamily C member 18;HNF 1A:HNF1 homeobox A;SLC 2A 11:Solute carrier family 2 member 11;PROM 2:Prominin 2;DPEP 1:Dipeptidase 1;TNFSF 8:TNF superfamily member 8;WNT 2B:Wnt family member 2B;ARSG:Arylsulfatase G;SPRR 2A:Small proline rich protein 2A;SPRR 2E:Small proline rich protein 2E;CAMK 2D:Calcium/calmodulin dependent protein kinaseⅡdelta;CDH 2:Cadherin 2;IFNLR 1:Interferon lambda receptor 1;IL 15RA:Interleukin 15 receptor subunit alpha.
【参考文献】：
期刊论文
[1]解毒散结方醇提物抗裸小鼠人肺癌术后转移作用的研究[J]. 郑婷婷,付艳丽,焦丽静,许玲. 中药新药与临床药理. 2016(06)
[2]解毒三根汤调节肿瘤相关成纤维细胞抗结肠癌侵袭转移及其对α-SMA、Sirt1、Ki67的影响[J]. 阮善明,孙钰,张恺,孙磊涛,沈敏鹤. 浙江中医药大学学报. 2016(03)
[3]肿瘤微环境的脾虚本质探讨[J]. 韩钦芮,符秀琼,禹志领,孙学刚. 中医杂志. 2014(04)
[4]5种不同治法中药对人肺癌A549细胞增殖的影响[J]. 周燕萍,杨航,关江峰,周良发,覃双来,徐坚,胡作为. 成都中医药大学学报. 2013(03)
[5]中西医两种方法评价肺瘤平膏联合化疗治疗中晚期非小细胞肺癌疗效[J]. 张培彤,林洪生,于明薇,杨宗艳,董海涛,张培宇,贺用和. 中医杂志. 2012(05)
[6]清热解毒法对小鼠Lewis肺癌瘤组织MMP-9及TIMP-1表达的影响[J]. 高静东,陈嘉璐,张蕾,刘敏,景天驰,李湧健. 江苏中医药. 2010(10)
[7]利用数据挖掘方法对肺癌中医药治疗特点的初步研究[J]. 刘杰,林洪生,侯炜,李道睿,周雪忠. 世界科学技术(中医药现代化). 2009(05)
[8]晚期肺癌中医辨证规律探讨[J]. 张学哲,张宁苏. 实用中医内科杂志. 2008(06)
[9]苦参注射液防治肺癌化疗毒副反应的临床观察[J]. 陶玉坚. 实用临床医药杂志. 2007(05)
硕士论文
[1]基于药对的不同治法对Lewis肺癌干预效应的比较研究[D]. 丁世宏.成都中医药大学 2018
[2]清热化痰散结方及其拆方抑制人肺癌细胞SK-MES和NCI-H69 PI3K-Akt-mTOR信号转导的研究[D]. 李萌萌.河南中医药大学 2016
[3]四组常用抗癌中药配伍抗lewis肺癌作用及其机制的比较研究[D]. 陈慧彬.中国人民解放军医学院 2014
本文编号：3265820
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