蠲瘤散結(jié)方抑制肺腺癌A549細(xì)胞移植瘤的增殖及可能作用機(jī)制的探討
發(fā)布時(shí)間：2021-07-05 09:31
目的:探討中藥蠲瘤散結(jié)方對(duì)荷人肺腺癌小鼠皮下移植瘤生長(zhǎng)的影響及可能的作用機(jī)制。方法:體外培養(yǎng)人肺腺癌A549細(xì)胞,采用皮下接種的方法構(gòu)建裸小鼠A549細(xì)胞移植瘤模型。實(shí)驗(yàn)分3組:對(duì)照組（0.9%的氯化鈉溶液）、順鉑（陽(yáng)性對(duì)照組）和蠲瘤散結(jié)方組,通過(guò)比較移植瘤體積和質(zhì)量等指標(biāo)觀察蠲瘤散結(jié)方對(duì)腫瘤生長(zhǎng)的影響。隨后,采用表達(dá)譜基因芯片技術(shù)檢測(cè)對(duì)照組和蠲瘤散結(jié)方組中各3個(gè)腫瘤樣本基因的表達(dá)水平,篩選差異表達(dá)的基因并進(jìn)行功能分析。結(jié)果:與對(duì)照組相比,順鉑組和蠲瘤散結(jié)方組移植瘤的質(zhì)量和體積均明顯降低,差異有統(tǒng)計(jì)學(xué)意義（P值均<0.05）;蠲瘤散結(jié)方組移植瘤的質(zhì)量和體積略高于順鉑組,但二組間差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）。蠲瘤散結(jié)方組小鼠的體質(zhì)量與對(duì)照組相比差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）,蠲瘤散結(jié)方組和對(duì)照組小鼠的體質(zhì)量都明顯高于順鉑組（P值均<0.05）。采用表達(dá)譜基因芯片技術(shù)檢測(cè)對(duì)照組和蠲瘤散結(jié)方組移植瘤中RNA的表達(dá)情況,共篩選獲得261個(gè)差異表達(dá)的基因,其中85個(gè)基因表達(dá)上調(diào),176個(gè)基因表達(dá)下調(diào)。對(duì)差異表達(dá)基因的分析顯示,蠲瘤散結(jié)方調(diào)控的差異基因多與代謝相關(guān),如...
【文章來(lái)源】：腫瘤. 2020,40(06)北大核心CSCD
【文章頁(yè)數(shù)】：9 頁(yè)
【部分圖文】：
采用差異表達(dá)基因聚類圖(A)和火山圖(B)分析蠲瘤散結(jié)方處理前后差異表達(dá)的基因
利用KEGG數(shù)據(jù)庫(kù)對(duì)差異基因進(jìn)行Pathway分析,并且用統(tǒng)計(jì)檢驗(yàn)的方法計(jì)算每個(gè)Pathway條目中差異基因富集的顯著性。整體差異基因的Pathway結(jié)果見圖4A,上調(diào)基因的Pathway結(jié)果見圖4B,下調(diào)基因的Pathway結(jié)果見圖4C。結(jié)果顯示,蠲瘤散結(jié)方調(diào)控的基因表達(dá)多與代謝相關(guān),如卵巢類固醇生成通路、糖脂代謝通路和視黃醇代謝通路等(表3)。這也與中醫(yī)藥治療腫瘤理論相應(yīng)證,提示應(yīng)從代謝的角度去分析中醫(yī)藥抑制腫瘤增殖和侵襲的具體機(jī)制。圖2 采用差異表達(dá)基因聚類圖(A)和火山圖(B)分析蠲瘤散結(jié)方處理前后差異表達(dá)的基因
表1 蠲瘤散結(jié)方處理后差異表達(dá)倍數(shù)變化最顯著的20個(gè)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 蠲瘤散結(jié)方處理后差異基因功能的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.
【參考文獻(xiàn)】：
期刊論文
[1]解毒散結(jié)方醇提物抗裸小鼠人肺癌術(shù)后轉(zhuǎn)移作用的研究[J]. 鄭婷婷,付艷麗,焦麗靜,許玲. 中藥新藥與臨床藥理. 2016(06)
[2]解毒三根湯調(diào)節(jié)腫瘤相關(guān)成纖維細(xì)胞抗結(jié)腸癌侵襲轉(zhuǎn)移及其對(duì)α-SMA、Sirt1、Ki67的影響[J]. 阮善明,孫鈺,張愷,孫磊濤,沈敏鶴. 浙江中醫(yī)藥大學(xué)學(xué)報(bào). 2016(03)
[3]腫瘤微環(huán)境的脾虛本質(zhì)探討[J]. 韓欽芮,符秀瓊,禹志領(lǐng),孫學(xué)剛. 中醫(yī)雜志. 2014(04)
[4]5種不同治法中藥對(duì)人肺癌A549細(xì)胞增殖的影響[J]. 周燕萍,楊航,關(guān)江峰,周良發(fā),覃雙來(lái),徐堅(jiān),胡作為. 成都中醫(yī)藥大學(xué)學(xué)報(bào). 2013(03)
[5]中西醫(yī)兩種方法評(píng)價(jià)肺瘤平膏聯(lián)合化療治療中晚期非小細(xì)胞肺癌療效[J]. 張培彤,林洪生,于明薇,楊宗艷,董海濤,張培宇,賀用和. 中醫(yī)雜志. 2012(05)
[6]清熱解毒法對(duì)小鼠Lewis肺癌瘤組織MMP-9及TIMP-1表達(dá)的影響[J]. 高靜東,陳嘉璐,張蕾,劉敏,景天馳,李湧健. 江蘇中醫(yī)藥. 2010(10)
[7]利用數(shù)據(jù)挖掘方法對(duì)肺癌中醫(yī)藥治療特點(diǎn)的初步研究[J]. 劉杰,林洪生,侯煒,李道睿,周雪忠. 世界科學(xué)技術(shù)(中醫(yī)藥現(xiàn)代化). 2009(05)
[8]晚期肺癌中醫(yī)辨證規(guī)律探討[J]. 張學(xué)哲,張寧蘇. 實(shí)用中醫(yī)內(nèi)科雜志. 2008(06)
[9]苦參注射液防治肺癌化療毒副反應(yīng)的臨床觀察[J]. 陶玉堅(jiān). 實(shí)用臨床醫(yī)藥雜志. 2007(05)
碩士論文
[1]基于藥對(duì)的不同治法對(duì)Lewis肺癌干預(yù)效應(yīng)的比較研究[D]. 丁世宏.成都中醫(yī)藥大學(xué) 2018
[2]清熱化痰散結(jié)方及其拆方抑制人肺癌細(xì)胞SK-MES和NCI-H69 PI3K-Akt-mTOR信號(hào)轉(zhuǎn)導(dǎo)的研究[D]. 李萌萌.河南中醫(yī)藥大學(xué) 2016
[3]四組常用抗癌中藥配伍抗lewis肺癌作用及其機(jī)制的比較研究[D]. 陳慧彬.中國(guó)人民解放軍醫(yī)學(xué)院 2014
本文編號(hào)：3265820
【文章來(lái)源】：腫瘤. 2020,40(06)北大核心CSCD
【文章頁(yè)數(shù)】：9 頁(yè)
【部分圖文】：
采用差異表達(dá)基因聚類圖(A)和火山圖(B)分析蠲瘤散結(jié)方處理前后差異表達(dá)的基因
利用KEGG數(shù)據(jù)庫(kù)對(duì)差異基因進(jìn)行Pathway分析,并且用統(tǒng)計(jì)檢驗(yàn)的方法計(jì)算每個(gè)Pathway條目中差異基因富集的顯著性。整體差異基因的Pathway結(jié)果見圖4A,上調(diào)基因的Pathway結(jié)果見圖4B,下調(diào)基因的Pathway結(jié)果見圖4C。結(jié)果顯示,蠲瘤散結(jié)方調(diào)控的基因表達(dá)多與代謝相關(guān),如卵巢類固醇生成通路、糖脂代謝通路和視黃醇代謝通路等(表3)。這也與中醫(yī)藥治療腫瘤理論相應(yīng)證,提示應(yīng)從代謝的角度去分析中醫(yī)藥抑制腫瘤增殖和侵襲的具體機(jī)制。圖2 采用差異表達(dá)基因聚類圖(A)和火山圖(B)分析蠲瘤散結(jié)方處理前后差異表達(dá)的基因
表1 蠲瘤散結(jié)方處理后差異表達(dá)倍數(shù)變化最顯著的20個(gè)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 蠲瘤散結(jié)方處理后差異基因功能的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.
【參考文獻(xiàn)】：
期刊論文
[1]解毒散結(jié)方醇提物抗裸小鼠人肺癌術(shù)后轉(zhuǎn)移作用的研究[J]. 鄭婷婷,付艷麗,焦麗靜,許玲. 中藥新藥與臨床藥理. 2016(06)
[2]解毒三根湯調(diào)節(jié)腫瘤相關(guān)成纖維細(xì)胞抗結(jié)腸癌侵襲轉(zhuǎn)移及其對(duì)α-SMA、Sirt1、Ki67的影響[J]. 阮善明,孫鈺,張愷,孫磊濤,沈敏鶴. 浙江中醫(yī)藥大學(xué)學(xué)報(bào). 2016(03)
[3]腫瘤微環(huán)境的脾虛本質(zhì)探討[J]. 韓欽芮,符秀瓊,禹志領(lǐng),孫學(xué)剛. 中醫(yī)雜志. 2014(04)
[4]5種不同治法中藥對(duì)人肺癌A549細(xì)胞增殖的影響[J]. 周燕萍,楊航,關(guān)江峰,周良發(fā),覃雙來(lái),徐堅(jiān),胡作為. 成都中醫(yī)藥大學(xué)學(xué)報(bào). 2013(03)
[5]中西醫(yī)兩種方法評(píng)價(jià)肺瘤平膏聯(lián)合化療治療中晚期非小細(xì)胞肺癌療效[J]. 張培彤,林洪生,于明薇,楊宗艷,董海濤,張培宇,賀用和. 中醫(yī)雜志. 2012(05)
[6]清熱解毒法對(duì)小鼠Lewis肺癌瘤組織MMP-9及TIMP-1表達(dá)的影響[J]. 高靜東,陳嘉璐,張蕾,劉敏,景天馳,李湧健. 江蘇中醫(yī)藥. 2010(10)
[7]利用數(shù)據(jù)挖掘方法對(duì)肺癌中醫(yī)藥治療特點(diǎn)的初步研究[J]. 劉杰,林洪生,侯煒,李道睿,周雪忠. 世界科學(xué)技術(shù)(中醫(yī)藥現(xiàn)代化). 2009(05)
[8]晚期肺癌中醫(yī)辨證規(guī)律探討[J]. 張學(xué)哲,張寧蘇. 實(shí)用中醫(yī)內(nèi)科雜志. 2008(06)
[9]苦參注射液防治肺癌化療毒副反應(yīng)的臨床觀察[J]. 陶玉堅(jiān). 實(shí)用臨床醫(yī)藥雜志. 2007(05)
碩士論文
[1]基于藥對(duì)的不同治法對(duì)Lewis肺癌干預(yù)效應(yīng)的比較研究[D]. 丁世宏.成都中醫(yī)藥大學(xué) 2018
[2]清熱化痰散結(jié)方及其拆方抑制人肺癌細(xì)胞SK-MES和NCI-H69 PI3K-Akt-mTOR信號(hào)轉(zhuǎn)導(dǎo)的研究[D]. 李萌萌.河南中醫(yī)藥大學(xué) 2016
[3]四組常用抗癌中藥配伍抗lewis肺癌作用及其機(jī)制的比較研究[D]. 陳慧彬.中國(guó)人民解放軍醫(yī)學(xué)院 2014
本文編號(hào)：3265820
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