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国家自然科学基金(30772859)

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苦参碱对人类肝癌细胞HepG2增殖、细胞周期及凋亡的影响被引量:11
2010年
目的探讨苦参碱(MT)对人类肝癌细胞株HepG2增殖、细胞周期及凋亡的影响。方法用不同质量浓度的MT(0.0125、0.025、0.05、0.1、0.2、0.4、0.8、1.6g/L)对培养的HepG2细胞作用不同时间(24、48、72h),用四氮噻唑蓝(MTT)比色法检测MT对细胞增殖的影响;流式细胞术(FCM)检测MT对HepG2细胞周期及凋亡的影响。结果质量浓度≥0.1g/L的MT有抑制HepG2细胞增殖的作用,且作用随药物质量浓度的增加及时间的延长而加强(P〈0.01)。FCM检测分析显示,0.8g/LMT作用48h能将HepG2细胞阻滞在G,期[(75.3±6.5)%对(64.1±6.3)%】(P〈0.05),1.6g/LMT作用48h能将HepG2细胞阻滞在G:期【(29.1±9.1)%对(11.6±2.1)%】(P〈0.01)。0.4、0.8、1.6g/LMT作用12、24、48h对HepG2细胞都有诱导凋亡作用,且作用随药物质量浓度的增加及作用时间的延长而加强(P〈0.01)。结论MT能够抑制HepG2细胞的增殖、诱导其凋亡并影响其细胞周期,呈时间和剂量依赖性。MT抗肝癌的机制可能与影响肝癌细胞周期、抑制细胞增殖及诱导凋亡有关。
朱丹丹姚树坤闫建国李红艳
关键词:肝肿瘤苦参碱细胞增殖细胞周期
清肝化瘀方药含药血清对肝癌SMMC-7721细胞基因组学影响被引量:3
2011年
目的从基因组学水平探讨清肝化瘀方药抗肿瘤的作用机制,以及丙酮预处理对抗癌中药含药血清的基因组学影响。方法采用血清药理学与基因组学技术相结合的方法,提取肝癌患者服用清肝化瘀方药前的血清以及服药6周后的含药血清,将服药前后的含药血清用丙酮法进行预处理。将丙酮法预处理的含药血清体外培养肝癌SMMC-7721细胞,通过对基因芯片上的32 050个探针组检测,分析全基因组基因的表达差异。结果服药后血清与服药前血清培养的细胞相比:基因表达上调≥2倍的有1 128个,基因表达下调≥2倍的有1 186个,分别占基因总数的3.52%、3.70%。差异表达的基因功能分类:上调的基因主要与信号传导途径、细胞凋亡有关;下调的基因主要与物质能量代谢、细胞增殖有关,差异表达的基因与抑制细胞生长有关。结论清肝化瘀方药肝癌患者的含药血清,通过影响人肝癌SMMC-7721细胞的信号转导、细胞增殖与凋亡等基因的表达,从多靶点发挥对肿瘤细胞生长的抑制作用。丙酮预处理含药血清对肿瘤细胞凋亡、物质能量代谢相关基因的表达影响较明显。
贺云妹殷飞姚树坤
关键词:清肝化瘀方药基因组学丙酮原发性肝癌
苦参碱对大鼠原发性肝癌防治作用及其机制的研究被引量:20
2010年
目的:研究苦参碱对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的大鼠原发性肝癌的防治作用及其可能的机制。方法:SD大鼠46只,模型组:21只,DEN35mg/kg灌胃,2次/周,共16周;苦参碱组:15只,DEN灌胃的同时给予苦参碱3mg/(kg.d)灌胃,共20周;空白对照组:10只,每日等体积生理盐水灌胃。大鼠肝脏HE染色观察病理改变,免疫组化SP法观察凋亡抑制蛋白Survivin、细胞周期蛋白Cyclin B1在肝脏的表达。结果:苦参碱组较模型组死亡率降低(40.0%vs76.2%),P<0.05;病理检查示,苦参碱组较模型组成癌率低(53.3%vs90.5%),P<0.05;免疫组化检测示,Survivin和Cyclin B1两种蛋白在模型组表达多,空白组表达少,苦参碱组表达较空白组多而较模型组少,苦参碱组与模型组比较差异有统计学意义,P<0.05。结论:苦参碱对DEN诱导大鼠原发性肝癌有防治作用,其机制可能与降低Survivin及Cyclin B1表达有关。
朱丹丹姚树坤闫建国潘琳李鸿
关键词:肝肿瘤苦参碱二乙基亚硝胺SURVIVINCYCLINB1
Diabetes mellitus: a “true” independent risk factor for hepatocellular carcinoma?被引量:23
2009年
BACKGROUND:Diabetes mellitus(DM)is thought to be associated with an increased risk of hepatocellular carcinoma(HCC)in some published studies.However,can we draw the conclusion that DM is a"true"independent risk factor for HCC based on these references? DATA SOURCES:MEDLINE and PubMed searches were conducted for published studies(between January 1966 and June 2009)to identify relevant articles using the keywords "diabetes","insulin resistance"and"hepatocellular carcinoma",including"primary liver cancer".Because of the very limited number of relevant articles most were reviewed. RESULTS:This systematic review was conducted from 4 aspects:(1)the significant synergy between DM,hepatitis virus infection,and heavy alcohol consumption in HCC; (2)the role of DM independently in HCC cases while other identified risk factors were controlled or excluded; (3)obesity,DM,and nonalcoholic fatty liver disease in HCC patients;and(4)the impact of DM for the prognosis or surgical treatment in HCC patients with DM.No consensus has been reached among these studies and it is too early to draw the conclusion that DM is a"true" independent risk factor for HCC. CONCLUSIONS:DM can be regarded as a risk factor for HCC.However,whether DM itself directly predisposes to HCC or whether it is a"true"independent risk factor remains unclear.Related issues should be clarified by more research.
Gao, ChunYao, Shu-Kun
关键词:DIABETESMELLITUSHEPATOCELLULAR
中医对原发性肝癌的辨证研究及治疗被引量:9
2010年
闫建国姚树坤
关键词:原发性肝癌中医中药治疗辨证研究肿瘤临床分期恶性肿瘤早期手术
血清药理学研究进展被引量:15
2009年
李静殷飞姚树坤
关键词:中药血清药理学给药方案采血时间
经乙醇处理后肝癌患者清肝化瘀方含药血清对肝癌细胞HepG2增殖的抑制作用被引量:2
2009年
目的:观察肝癌患者清肝化瘀方含药血清经乙醇处理后对肝癌细胞增殖的抑制作用。方法:肝癌患者分别于服清肝化瘀方前、服药2周、4周、6周服药后2h静脉采血10ml,分离血清。预处理(向血清内加入4倍量的乙醇混匀,3000r/min离心,取上清温水浴蒸发,除去乙醇)。采用四唑盐比色法(简称MTT)比较经乙醇处理后含药血清对肝癌细胞HepG2增殖的抑制作用。结果:随着患者用药时间延长和培养时间延长,抑制率逐渐增强。未处理血清抑制率最高可达36.2%,经乙醇处理血清抑制率最高可达33.2%。结论:经处理后肝癌患者清肝化瘀方含药血清对肝癌细胞增殖有较强的抑制作用,但抑制率较未处理组弱。
姚树坤殷飞李静
关键词:清肝化瘀方中药血清药理学乙醇
Potential role of diabetes mellitus in the progression of cirrhosis to hepatocellular carcinoma:a cross-sectional case-control study from Chinese patients with HBV infection被引量:8
2013年
BACKGROUND: Diabetes mellitus (DM) is regarded as a new risk factor for hepatocellular carcinoma (HCC), but few studies have focused on the potential role of DM in the progression of cirrhosis to HCC as well as in patients with simple HBV infection. METHODS: A cohort of 1028 patients, treated at our hospital and with a hospital discharge diagnosis of HCC and/or cirrhosis, was screened. Among them, 558 were diagnosed with chronic HBV infection and 370 were analyzed statistically according to the diagnostic, inclusion and exclusion criteria. The demographic, clinical, metabolic, virological, biochemical, radiological and pathological features were analyzed and the multivariate logistic regression model was used to determine the potential role of DM. RESULTS: In 248 cirrhotic patients, 76 were diabetic and their mean duration of DM was 4.6 years. In 122 HCC patients with cirrhosis, 25 were diabetic and their mean duration of DM was 4.4 years. Univariate analysis showed that compared with cirrhotic patients, the HCC patients had a higher percentage in males (P=0.001), a lower percentage in DM patients (P=0.039), a higher percentage in cigarette smokers (P=0.005), a higher percentage in patients with AFP>400 ng/mL (P<0.001), higher values of white blood cells (P<0.001), hemoglobin (P<0.001) and platelet (P<0.001), increased levels of ALT (P<0.001) and GGT (P<0.001), higher total bilirubin (P=0.018) and albumin levels (P<0.001), and a lower international normalized ratio (P<0.001). Multivariate logistic regression analysis showed that DM was anindependent associated factor for HCC [odds ratio (OR)=0.376; 95% CI, 0.175-0.807; P=0.012]. Even after the HCC patients were restricted to those with decompensated cirrhosis and compared with decompensated cirrhotic patients, the similar result was observed (OR=0.192; 95% CI, 0.054-0.679; P=0.010). CONCLUSIONS: DM is an independent factor in the progression of cirrhosis to HCC, but the role may be contrary to our current viewpoint. To clarify the causal relationship of DM and HC
Chun GaoLong FangHong-Chuan ZhaoJing-Tao LiShu-Kun Yao
关键词:MELLITUSHEPATOCELLULARCIRRHOSIS
苦参碱对人肝癌细胞HepG2荷瘤裸鼠的抑瘤作用研究被引量:10
2016年
目的研究苦参碱对人肝癌细胞HepG2荷瘤裸鼠的抑瘤作用及其作用机制。方法 BALB/C裸鼠随机分为对照组和苦参碱25、50、75 mg/kg组,每组各10只。建立裸鼠肝癌细胞HepG2移植瘤模型。对照组ip生理盐水1 mL,1次/d;苦参碱25、50、75 mg/kg组分别ip 0.5、1.0、1.5 mg/mL苦参碱溶液1 mL,1次/d。连续给药35 d。计算瘤体体积和肿瘤体积抑制率。观察裸鼠瘤体HE染色病理改变和免疫组化染色,测定各组裸鼠瘤体Survivin蛋白表达量,并采用RT-PCR法检测裸鼠瘤体Survivin mRNA相对表达量。结果与对照组比较,苦参碱50、75 mg/kg组裸鼠瘤体体积显著减小(P<0.01);苦参碱组裸鼠瘤体生长速度较对照组减慢,肝癌细胞分布较对照组稀疏,且剂量越大越明显。苦参碱50、75 mg/kg组仅有少量Survivin表达于细胞质。与对照组比较,苦参碱50、75 mg/kg组裸鼠Survivin蛋白表达量和Survivin mRNA相对表达量显著减小(P<0.01)。结论苦参碱对人肝癌细胞HepG2荷瘤裸鼠具有抑瘤作用,有效剂量为50 mg/kg,其机制可能与下调Survivin表达、诱导肝癌细胞凋亡有关。
朱丹丹姚树坤
关键词:苦参碱人肝癌细胞HEPG2SURVIVIN表达
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