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MicroRNA-185通过靶向调节DN-MT1/PTEN/Akt通路抑制肝细胞癌的生长 被引量:12
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作者 Qadir X V han c +2 位作者 Lu D 魏建国 许春伟 《临床与实验病理学杂志》 CAS CSCD 北大核心 2014年第12期1364-1364,共1页
近来研究表明miRNAs与肝癌的发生密切相关,然而单个miRNAs的具体作用机制仍未完全阐明。作者对microR-NA-185(miR-185)在肝细胞癌生物学功能和分子机制方面做了一些研究。实验发现,与非肿瘤性的肝脏实质相比, miR-185在人肝细胞癌组... 近来研究表明miRNAs与肝癌的发生密切相关,然而单个miRNAs的具体作用机制仍未完全阐明。作者对microR-NA-185(miR-185)在肝细胞癌生物学功能和分子机制方面做了一些研究。实验发现,与非肿瘤性的肝脏实质相比, miR-185在人肝细胞癌组织中的表达减少;qRT-PCR检测显示,与原代肝细胞相比, miR-185在人肝细胞癌细胞中的表达下降;在体外人肝细胞癌细胞中miR-185的过表达会抑制细胞的增殖和侵袭,并且阻止SCID小鼠体内肿瘤的生长。miR-185的过表达能够抑制肝细胞癌细胞中DNMT13′端非翻译区域荧光素酶的活性,当 miR-185结合位点发生突变时,就不存在该效应;miR-185的复制或过表达会减少肝细胞癌细胞中DNMT1蛋白的表达。这些结果表明DNMT1是miR-185在肝细胞癌细胞中的靶向作用蛋白。 DNMT1在miR-185诱导抑制肝细胞癌的增殖中所起的作用,可进一步通过DNMT1的过表达阻止miR-185诱导抑制肝细胞癌细胞的增殖和侵袭这一事实所证实。 miR-185的复制或过表达能够减少PTEN启动子DNA甲基化并且提高PTEN的表达,从而抑制Akt磷酸化;如果DNMT1过表达,这些效应刚好相反。以上结果表明:miR-185靶向作用于DNMT1,通过诱导PTEN和抑制Akt,从而抑制肝细胞癌细胞的增殖,活化或激活miR-185可能成为肝细胞癌新的治疗策略之一。 展开更多
关键词 肝细胞癌组织 AKT通路 靶向作用 生长 肝细胞癌细胞 PTEN启动子 DNMT1 MIRNAS
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Chemoprevention of tea on colorectal cancer induced by dimethylhydrazine in Wistar rats 被引量:21
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作者 Jia XD han c 《World Journal of Gastroenterology》 SCIE CAS CSCD 2000年第5期699-703,共5页
AIM To investigate the chemopreventiveeffects of green tea and tea pigment on 1,2-dimethylhydrazine(DMH)-induced rat colorectalcarcinogenesis.METHODS Male weaning Wistar rats wererandomly allocated into four groups.Ra... AIM To investigate the chemopreventiveeffects of green tea and tea pigment on 1,2-dimethylhydrazine(DMH)-induced rat colorectalcarcinogenesis.METHODS Male weaning Wistar rats wererandomly allocated into four groups.Rats in thepositive control group were given s.c.injectionof DMH,once a week for ten weeks;rats in tea-treated groups,with the same DMH treatment asin the positive group,received 2% green tea and0.1% tea pigments;rats in the negative controlgroup were given s.c.injection of the samevolume of saline as well as DMH in the positivegroup.Animals were sacrified and necropsied atthe end of week 16 and week 32.RESULTS Aberrant cryptic foci(ACF)wereformed in animals in DMH-treated groups at theend of week 16.Compared to the DMH group,green tea and tea pigments groups had less ACF(148.25 and 204.25,respectively,P【0.01).Atthe end of week 32,all rats in DMH groupdeveloped large intestinal tumors.The resultsalso showed that DMH increased labeling index(LI)of proliferating cell nuclear antigen(PCNA)of intestinal mucosa and the expression of ras-p21.However,in the tea-treated groups,PCNA-LI was significantly reduced as compared withthe positive control group(36.63 and 40.36 inthe green tea group and tea pigment group,respectively,at the end of the experiment,P【0.01).ras-p21 expression was alsosignificantly reduced(2.07 and 2.36 in the colontumors of rats in the green tea group and teapigments group,respectively at the end of theexperiment,P【0.01).Furthermore,green tea and tea pigment inhibited the expression of Bcl-2protein(2,5,1,0 and 2,4,1,0,respectively,at the end of the experiment P【0.01),andinduced expression of Bax protein(0,1,3,4and 0,1,4,3,respectively,P【0.01).CONCLUSION Chinese green tea drinkinginhibited ACF and colonic tumors formation inrats,which showed that tea had a significantchemopreventive effect on DMH-inducedcolorectal carcinogenesis.Such effects may bedue to suppression of cell proliferation andinduction of apoptosis in the intestinal crypts. 展开更多
关键词 colorectal neoplasms DIMETHYLHYDRAZINE TEA apoptosis aberant CRYPT FOCI rats PROLIFERATING cell nuclear antigen CHEMOPREVENTION
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