白藜芦醇调控胃癌发生研究进展
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摘要
胃癌(Gastric cancer)是一种起源于胃黏膜上皮的恶性肿瘤,也是世界上常见的几种癌症之一。亚洲尤其是中国是胃癌的高发区,中国每年的胃癌患病率和死亡率均高于世界平均水平。尽管个性化预防和治疗可降低患者死亡率,但幽门螺杆菌基因型、宿主基因多态性、癌细胞耐药性等诸多因素使得药物预防和治疗效果不明显。白藜芦醇(Resveratrol,Res)是一种广泛存在于植物中的二苯乙烯类化合物,具有抗肿瘤、抗氧化、抗炎、防治心血管疾病、抗真菌、延年益寿等多种药理学功效,尤其对肝癌、结肠癌、肺癌等癌症具有很好的治疗效果,但其在胃癌的特异性靶点、药物和发生通路等方面的研究较少,文章就白藜芦醇在胃癌防治方面的最新研究成果进行总结,将为胃癌药物研发提供新靶点和思路。
Gastric cancer is the malignant tumor originated from the epithelium of stomach,and also one of the most lethal cancers in the world. Asia,especially China,is a prevalent area of gastric cancer. The annual morbidity and mortality of gastric cancer in China is higher than the world average level. Although individualized prophylaxis and treatment can reduce the mortality rate,factors including the genotype of Helicobacter pylori,host gene polymorphism and drug resistance of cancer cell make the effect of drug prevention and treatment unobvious. Resveratrol( Res) is a stilbene compound which widely exists in plants. It possesses plenty of pharmacological effects including anti-tumor,anti-oxidation,anti-inflammatory,prevention and treatment in cardiovascular diseases,anti-fungal,and longevity enhancement. Although Res has good therapeutic effects on liver cancer,colon cancer and lung cancer,few pharmacological researches in gastric cancer have carried out it respect to the specific targets,drug interactions and anti-tumor pathways. This article has summarized the latest research results of Resin the prevention and treatment of gastric cancer,wishing to provide some new targets and ideas for drug research and development.
Gastric cancer is the malignant tumor originated from the epithelium of stomach,and also one of the most lethal cancers in the world. Asia,especially China,is a prevalent area of gastric cancer. The annual morbidity and mortality of gastric cancer in China is higher than the world average level. Although individualized prophylaxis and treatment can reduce the mortality rate,factors including the genotype of Helicobacter pylori,host gene polymorphism and drug resistance of cancer cell make the effect of drug prevention and treatment unobvious. Resveratrol( Res) is a stilbene compound which widely exists in plants. It possesses plenty of pharmacological effects including anti-tumor,anti-oxidation,anti-inflammatory,prevention and treatment in cardiovascular diseases,anti-fungal,and longevity enhancement. Although Res has good therapeutic effects on liver cancer,colon cancer and lung cancer,few pharmacological researches in gastric cancer have carried out it respect to the specific targets,drug interactions and anti-tumor pathways. This article has summarized the latest research results of Resin the prevention and treatment of gastric cancer,wishing to provide some new targets and ideas for drug research and development.
引文
[1]向培,陈艳,潘棋,等.胃癌细胞中CEACAM1和MMP-2的表达及意义[J].药物生物技术,2018,25(1):31-33.
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[3]Li-Ping P,Si-Li Y,Chang-Jian C,et al.Cloning a peanut resveratrol synthase gene and its expression in purple sweet potato[J].Plant Cell Rep,2012,31(1):121-131.
[4]Zong Y,Sun L,Liu B,et al.Resveratrol inhibits LPS-induced MAPKs activation via activation of the phosphatidylinositol 3-kinase pathway in murine RAW 264.7 macrophage cells[J].PloS one,2012,7(8):e44107.
[5]Wang S,Jiang L,Xing L,et al.Resveratrol inhibits proliferation of human gastric cancer MGC803 cells via regulating TGFβ1/Smad signaling pathways[J].J Modern Oncol,2016.
[6]Liu Z,Chen Z,Fan R,et al.Over-expressed long noncoding RNAHOXA11-AS promotes cell cycle progression and metastasis in gastric cancer[J].Molec Cancer,2017,16(1):82-82.
[7]Shi X,Sun M,Liu H,et al.Long non-coding RNAs:a new frontier in the study of human diseases[J].Cancer Lett,2013,339(2):159-166.
[8]Parsonnet J,Friedman GD,Vandersteen DP,et al.Helicobacter pylori infection and the risk of gastric carcinoma[J].N Engl JMed,1991,325(16):1127-1131.
[9]Pandey S,Jha HC,Shukla SK,et al.Epigenetic regulation of tumor suppressors by helicobacter pylori enhances EBV-induced proliferation of gastric epithelial cells[J].m Bio,2018,9(2):e00649-00618.
[10]张振华,侯海金,张斌,等.白藜芦醇通过调控Wnt/β-catenin信号通路抑制体外胃癌细胞生长的研究[J].中华临床医师杂志,2017,11(15):2087-2092.
[11]Reya T,Clevers H.Wnt signalling in stem cells and cancer[J].Nature,2005,434:843-850.
[12]王玲琳,朱妍,朴花子.白藜芦醇对CXCL12诱导的胃癌细胞增殖的影响[J].肿瘤药学,2015(2):101-105.
[13]Yang T,Zhang J,Zhou J,et al.Resveratrol inhibits Interleukin-6induced invasion of human gastric cancer cells[J].Biomed Pharmacother,2018,99:766-773.
[14]Brown GT,Murray GI.Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis[J].J Pathol,2015,237(3):273-281.
[15]Wagner RJ,Martin KA,Powell RJ,et al.Lovastatin induces VSMC differentiation through inhibition of Rheb and m TOR[J].Am J Physiol Cell Physiol,2010,299(1):119-127.
[16]孙龙和,夏建国,钱春华,等.白藜芦醇通过Pi3K/AKT通路抑制胃癌SGC-7901细胞增殖和迁移[J].现代生物医学进展,2016,16(17):3237-3240.
[17]Reis-Sobreiro M,Gajate C,Mollinedo F.Involvement of mitochondria and recruitment of Fas/CD95 signaling in lipid rafts in resveratrol-mediated antimyeloma and antileukemia actions[J].Oncogene,2009,28(36):3221-3234.
[18]舒洋,陈实.不同浓度白藜芦醇对人骨肉瘤细胞MG-63增殖、凋亡的影响及机制研究[J].实用医学杂志,2018,34(7):58-62.
[19]Wu X,Xu Y,Zhu B,et al.Resveratrol induces apoptosis in SGC-7901 gastric cancer cells[J].Oncol Lett,2018,16(3):2949-2956.
[20]Gasparini C,Celeghini C,Monasta L,et al.NF-κB pathways in hematological malignancies[J].Cellul Molec Life Sci,2014,71(11):2083-2102.
[21]Catz SD,Johnson JL.Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer[J].Oncogene,2001,20(50):7342-7351.
[22]海洋,李建银,王欣,等.雄黄微生物浸出液通过线粒体途径诱导人急性髓系白血病细胞HL60细胞凋亡[J].药物生物技术,2018,25(4):5-9.
[23]Yang Y,Huang X,Chen S,et al.Resveratrol induced apoptosis in human gastric carcinoma SGC-7901 cells via activation of mitochondrial pathway[J].Asia Pacific J Clin Oncol,2018,14(5):e317-e324.
[24]王阿曼,宁振,刘基巍.非小细胞肺癌EGFR-TKI耐药的分子机制及防治策略[J].中华肿瘤防治杂志,2017,24(1):71-78.
[25]彭秋霞,范娟,韩云炜.阿帕替尼治疗恶性肿瘤的研究进展[J].西南军医,2017,19(2):176-179.
[26]Li Jun CF,Cheng Dan,Jia Xiaoyan,et al.Experimental study of resveratrol reverses the resistance of gastric cancer cells to apatinib[J].Chinese Clin Oncol,2018,23:790-794.
[27]Xu J,Liu D,Niu H,et al.Resveratrol reverses doxorubicin resistance by inhibiting epithelial-mesenchymal transition(EMT)through modulating PTEN/Akt signaling pathway in gastric cancer[J].J Exper Clin Cancer Res,2017,36(1):19-19.
[28]Jing X,Cheng W,Wang S,et al.Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway[J].Oncol Rep,2016,35(1):472-478.
[29]Mieszala K,Rudewicz M,Gomulkiewicz A,et al.Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol[J].Oncol Lett,2018,15(4):5825-5832.
[30]Kartalyandim M,Adangokbulut A,Baran Y.Molecular mechanisms of drug resistance and its reversal in cancer[J].Critic Rev Biotechnol,2016,36(4):1-11.
[2]Torre L A,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].Ca A Cancer J Clin,2015,65(2):87-108.
[3]Li-Ping P,Si-Li Y,Chang-Jian C,et al.Cloning a peanut resveratrol synthase gene and its expression in purple sweet potato[J].Plant Cell Rep,2012,31(1):121-131.
[4]Zong Y,Sun L,Liu B,et al.Resveratrol inhibits LPS-induced MAPKs activation via activation of the phosphatidylinositol 3-kinase pathway in murine RAW 264.7 macrophage cells[J].PloS one,2012,7(8):e44107.
[5]Wang S,Jiang L,Xing L,et al.Resveratrol inhibits proliferation of human gastric cancer MGC803 cells via regulating TGFβ1/Smad signaling pathways[J].J Modern Oncol,2016.
[6]Liu Z,Chen Z,Fan R,et al.Over-expressed long noncoding RNAHOXA11-AS promotes cell cycle progression and metastasis in gastric cancer[J].Molec Cancer,2017,16(1):82-82.
[7]Shi X,Sun M,Liu H,et al.Long non-coding RNAs:a new frontier in the study of human diseases[J].Cancer Lett,2013,339(2):159-166.
[8]Parsonnet J,Friedman GD,Vandersteen DP,et al.Helicobacter pylori infection and the risk of gastric carcinoma[J].N Engl JMed,1991,325(16):1127-1131.
[9]Pandey S,Jha HC,Shukla SK,et al.Epigenetic regulation of tumor suppressors by helicobacter pylori enhances EBV-induced proliferation of gastric epithelial cells[J].m Bio,2018,9(2):e00649-00618.
[10]张振华,侯海金,张斌,等.白藜芦醇通过调控Wnt/β-catenin信号通路抑制体外胃癌细胞生长的研究[J].中华临床医师杂志,2017,11(15):2087-2092.
[11]Reya T,Clevers H.Wnt signalling in stem cells and cancer[J].Nature,2005,434:843-850.
[12]王玲琳,朱妍,朴花子.白藜芦醇对CXCL12诱导的胃癌细胞增殖的影响[J].肿瘤药学,2015(2):101-105.
[13]Yang T,Zhang J,Zhou J,et al.Resveratrol inhibits Interleukin-6induced invasion of human gastric cancer cells[J].Biomed Pharmacother,2018,99:766-773.
[14]Brown GT,Murray GI.Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis[J].J Pathol,2015,237(3):273-281.
[15]Wagner RJ,Martin KA,Powell RJ,et al.Lovastatin induces VSMC differentiation through inhibition of Rheb and m TOR[J].Am J Physiol Cell Physiol,2010,299(1):119-127.
[16]孙龙和,夏建国,钱春华,等.白藜芦醇通过Pi3K/AKT通路抑制胃癌SGC-7901细胞增殖和迁移[J].现代生物医学进展,2016,16(17):3237-3240.
[17]Reis-Sobreiro M,Gajate C,Mollinedo F.Involvement of mitochondria and recruitment of Fas/CD95 signaling in lipid rafts in resveratrol-mediated antimyeloma and antileukemia actions[J].Oncogene,2009,28(36):3221-3234.
[18]舒洋,陈实.不同浓度白藜芦醇对人骨肉瘤细胞MG-63增殖、凋亡的影响及机制研究[J].实用医学杂志,2018,34(7):58-62.
[19]Wu X,Xu Y,Zhu B,et al.Resveratrol induces apoptosis in SGC-7901 gastric cancer cells[J].Oncol Lett,2018,16(3):2949-2956.
[20]Gasparini C,Celeghini C,Monasta L,et al.NF-κB pathways in hematological malignancies[J].Cellul Molec Life Sci,2014,71(11):2083-2102.
[21]Catz SD,Johnson JL.Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer[J].Oncogene,2001,20(50):7342-7351.
[22]海洋,李建银,王欣,等.雄黄微生物浸出液通过线粒体途径诱导人急性髓系白血病细胞HL60细胞凋亡[J].药物生物技术,2018,25(4):5-9.
[23]Yang Y,Huang X,Chen S,et al.Resveratrol induced apoptosis in human gastric carcinoma SGC-7901 cells via activation of mitochondrial pathway[J].Asia Pacific J Clin Oncol,2018,14(5):e317-e324.
[24]王阿曼,宁振,刘基巍.非小细胞肺癌EGFR-TKI耐药的分子机制及防治策略[J].中华肿瘤防治杂志,2017,24(1):71-78.
[25]彭秋霞,范娟,韩云炜.阿帕替尼治疗恶性肿瘤的研究进展[J].西南军医,2017,19(2):176-179.
[26]Li Jun CF,Cheng Dan,Jia Xiaoyan,et al.Experimental study of resveratrol reverses the resistance of gastric cancer cells to apatinib[J].Chinese Clin Oncol,2018,23:790-794.
[27]Xu J,Liu D,Niu H,et al.Resveratrol reverses doxorubicin resistance by inhibiting epithelial-mesenchymal transition(EMT)through modulating PTEN/Akt signaling pathway in gastric cancer[J].J Exper Clin Cancer Res,2017,36(1):19-19.
[28]Jing X,Cheng W,Wang S,et al.Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway[J].Oncol Rep,2016,35(1):472-478.
[29]Mieszala K,Rudewicz M,Gomulkiewicz A,et al.Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol[J].Oncol Lett,2018,15(4):5825-5832.
[30]Kartalyandim M,Adangokbulut A,Baran Y.Molecular mechanisms of drug resistance and its reversal in cancer[J].Critic Rev Biotechnol,2016,36(4):1-11.