白术内酯Ⅰ对人胃癌细胞SGC-7901裸鼠移植瘤生长及凋亡的影响
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摘要
目的:研究白术内酯Ⅰ(atractylenolideⅠ)对人胃癌细胞SGC-7901裸鼠移植瘤生长及凋亡相关蛋白Bax、cleaved caspase-3、p53、Bcl-2表达的影响。方法:建立SGC-7901裸鼠移植瘤模型,观察白术内酯Ⅰ对肿瘤生长的影响;TUNEL法检测移植瘤组织中的细胞凋亡;Western blotting检测瘤组织中Bax、Bcl-2、cleaved caspase-3及p53蛋白表达。结果:白术内酯Ⅰ不同程度抑制裸鼠SGC-7901移植瘤的生长,与对照组比较,给药后肿瘤体积(TV,tumor volume)、相对肿瘤体积(RTV,relative tumor volume)和相对肿瘤增殖率[T/C(%),TRTV/CRTV]明显下降;移植瘤组织中凋亡细胞明显增多;白术内酯Ⅰ上调移植瘤组织中Bax、cleaved caspase-3及p53的蛋白表达,下调Bcl-2的蛋白表达。结论:白术内酯Ⅰ能明显抑制人胃癌细胞SGC-7901裸鼠移植瘤的生长,分子机制主要包括增加Bax、cleaved caspase-3、p53蛋白表达,减少Bcl-2蛋白表达,最终导致肿瘤细胞凋亡。
OBJECTIVE To investigate the effect of atractylenolideⅠ on the growth and expression of apoptosis related proteins involving Bax,cleaved caspase-3,p53 and Bcl-2 in human gastric cancer cell line SGC-7901 xenografts in nude mice.METHODS The model of nude mice with SGC-7901 cell was established significantly in the treatment group.The cell apoptosis of transplant tumor tissue increased as detected by the TUNEL assay.The expression of proteins including Bcl-2,Bax,cleaved caspase-3 and p53 were determined by Western blotting assay.RESULTS AtractylenolideⅠinhibited the growth of xenografts in nude mice.Compared with control group,TV(tumor volume),RTV(relative tumor volume)and T/C(%)(TRTV/CRTV)decreased after treatment with atractylenolide I.The apoptosis cells were elevated after treatment with atractylenolidesⅠ.Western blotting showed that several proteins including Bax,cleaved caspase-3 and p53 were up-regulated after treatment with atractylenolidesⅠ,however,the expression of Bcl-2 protein inversed in the transplant tumor tissues.CONCLUSION Atractylenolide I significantly inhibits the growth of SGC-7901 cell xenografts in nude mice,which may be caused by inducing tumor cell apoptosis by up-regulation of Bax,cleaved caspase-3,p53 expressions and down-regulation of Bcl-2 expression.
OBJECTIVE To investigate the effect of atractylenolideⅠ on the growth and expression of apoptosis related proteins involving Bax,cleaved caspase-3,p53 and Bcl-2 in human gastric cancer cell line SGC-7901 xenografts in nude mice.METHODS The model of nude mice with SGC-7901 cell was established significantly in the treatment group.The cell apoptosis of transplant tumor tissue increased as detected by the TUNEL assay.The expression of proteins including Bcl-2,Bax,cleaved caspase-3 and p53 were determined by Western blotting assay.RESULTS AtractylenolideⅠinhibited the growth of xenografts in nude mice.Compared with control group,TV(tumor volume),RTV(relative tumor volume)and T/C(%)(TRTV/CRTV)decreased after treatment with atractylenolide I.The apoptosis cells were elevated after treatment with atractylenolidesⅠ.Western blotting showed that several proteins including Bax,cleaved caspase-3 and p53 were up-regulated after treatment with atractylenolidesⅠ,however,the expression of Bcl-2 protein inversed in the transplant tumor tissues.CONCLUSION Atractylenolide I significantly inhibits the growth of SGC-7901 cell xenografts in nude mice,which may be caused by inducing tumor cell apoptosis by up-regulation of Bax,cleaved caspase-3,p53 expressions and down-regulation of Bcl-2 expression.
引文
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[3]Pan LW,Song J.Atractylodes lactone I the resistance of melanoma in vivo and in vitro studies[J].Chin Hosp Pharm J(中国医院药学杂志),2015,35(8):682-685.
[4]Qiu GQ,Zhao XS,Sun Y,et al.Experimental study on the influence of volatile oil from atractylodes macrocephala on TNF-αand IL-6in cancer cachexia[J].J Xi'an Jiaotong Univ Med Sci(西安交通大学学报:医学版),2006,27(5):477-479.
[5]Cai Y,Sun Y,Liu Y,et al.Effect of volatile oil on serum cytokines TNF-alpha and IL-2 in cancer patients[J].Shaanxi J Tradit Chin Med(陕西中医),2006,27(11):1432-1434.
[6]Tang SC,Pan H,Huang YY,et al.Establishment of the model of human non-small cell lung cancer xenograft model[J].J Kunming Med Univ(昆明医科大学学报),2017,38(2):28-32.
[7]Sai Y,Liu Y,Dong ZJ.The key protein activity regulation in apoptosis mechanism and the new drug design of clinical disease[J].Mod Med Heal(现代医药卫生),2003,19(6):690-692.
[8]Yang J,Zhao XY,Tang M,et al.The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of ovarian cancer cells[J].Oncotarget,2017,8(14):23492-23506.
[9]Ribeiro SC,Muratori M,De Geyter M,et al.TUNEL labeling with BrdUTP/anti-BrdUTP greatly underestimates the level of sperm DNA fragmentation in semen evaluation[J].PLoS One,2017,12(8):e0181802.
[10]Liu SN,Sao SL,Sui WJ,et al.Resveratrol induced apoptosis of A549 cells in lung cancer[J].Genom Appl Biol(基因组学与应用生物学),2015,34(4):685-691.
[11]Meng TJ,Jiang YL,Yan XY,et al.Effect of fructus schizandrae polysaccharide on apoptosis of human glioma cells[J].J Jilin Med Coll(吉林医药学院学报),2014,35(4):254-257.
[12]Bi DB,Yang MS,Zhao X,et al.Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model[J].Med Sci Monit,2015,21:2421-2427.
[13]Jiang Y,Xu HJ,Wang JF.Alantolactone induces apoptosis of human cervical cancer cells via reactive oxygen species generation,glutathione depletion and inhibition of the Bcl-2/Bax signaling pathway[J].Oncol Lett,2016,11(6):4203-4207.
[14]Joseph Mazar,Amy Rosado,John Shelley,et al.The long noncoding RNA GAS5 differentially regulates cell cycle arrest and apoptosis through activation of BRCA1 and p53in human neuroblastoma[J].Oncotarget,2017,8(4):6589-6607.
[15]Zhu YX,Zhao MX.The expression of bcl-2 apoptosis gene Bax in gastric cancer and precancerous lesion was inhibited by the suppressor gene p53 apoptosis[J].Chin J Gastroenter Hepatol(胃肠病学和肝病学杂志),2016,25(9):1040-1043.