PTEN蛋白表达与胃癌预后的关系探讨

目的探讨胃癌细胞PTEN蛋白表达与病理类型和胃癌预后的关系。方法检测胃癌患者癌细胞PTEN蛋白表达情况,分析胃癌细胞生物学行为与预后的关系。结果 PTEN蛋白表达缺失患者的1.5年生存率低于PTEN蛋白表达患者(P<0.01);生存期≥1.5年的胃癌患者PTEN蛋白表达阳性率(67.6%)高于生存期<1.5年者(22.6%)(P<0.05);无转移的胃癌患者PTEN蛋白表达阳性率高于有转移者(P<0.05)。结论 PTEN蛋白表达可作为预测胃癌预后有价值的标志物。

PTEN基因在非小细胞肺癌中表达的临床研究

目的研究PTEN基因在人非小细胞肺癌中表达情况，探讨PTEN基因在人肺癌发生、发展过程中的可能作用。方法采用免疫组化方法检测143例非小细胞肺癌、20例正常肺组织及良性病变中PTEN蛋白表达情况。结果在正常肺组织及肺良性病变组织中无失表达：肺癌组织中失表达率57．34％（82／143），两者比较有显著性差异（P〈0．001）；肺癌组织中PTEN基因表达水平与肿瘤细胞分化程度、TNM分期、淋巴结转移程度存在相关性（P〈0．001）；PTEN蛋白失表达组．肺癌患者的术后五年生存率显著低于表达组（P〈0．001）；吸烟组患者PTEN基因失表达率显著高于无吸烟组（P〈0．001）。结论PTEN蛋白失表达与肺癌的发生、发展及预后有关；多因素分析PTEN基因失表达是影响非小细胞肺癌预后的独立因素。

Relation of overexpression of S phase kinase-associated protein 2 with reduced expression of p27 and PTEN in human gastric carcinoma

AIM： TO investigate the significance of S phase kinase- associated protein 2 （Skp2） expression in human gastric carcinoma and the relation between expressions of Skp2, p27 and PTEN. METHODS： Immunohistochemical analysis was performed on 138 gastric carcinoma specimens, their paired adjacent mucosa specimens, 102 paired lymphatic metastatic carcinoma tissue specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, 10 chronic superficial gastritis specimens and 5 normal gastric mucosa specimens for Skp2 expression and on 138 gastric carcinoma specimens for p27 and PTEN expression. RESULTS： Skp2 labeling frequency was significantly higher in intestinal rnetaplasia （12.68±0.86） and adjacent rnucosa （19.324±1.22） than in normal gastric rnucosa （0.53±0.13） and chronic superficial gastritis （0.47±0.19） （P = 0.000）, in dysplasia （16.74±0.82）than in intestinal metaplasia （P = 0.000）; in gastric primary carcinoma （31.34±2.17） than in dysplasia and adjacent rnucosa （P = 0.000）, in metastasis gastric carcinoma in lymph nodes （39.76±2.00） than in primary gastric carcinoma （P = 0.037）, respectively. Skp2 labeling frequency was positively associated with differentiation degree （rho = 0.315, P = 0.000）, vessel invasion （rho = 0.303, P = 0.000） and lymph node metastasis （rho = 0.254, P = 0.000） of gastric cancer. Expression of Skp2 was negatively associated with p27 （rho = -0.451, P = 0.000） and PTEN （rho = -0.480, P = 0.000） expression in gastric carcinoma, p27 expression was positively associated with PTEN expression in gastric carcinoma （rho = 0.642, P = 0.000）.CONCLUSION： Skp2 overexpression may be involvedin carcinogenesis and progression of human gastric carcinoma in vivo, possibly via p27 proteolysis. PTEN may regulate the expression of p27 by negatively regulating Skp2 expression.

Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts in nude mice

AIM:To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude mice.METHODS: Nude mice bearing HuH7 xenografts were used to assess the anti-HCC effects and mechanisms of silibinin.RESULTS: Silibinin resulted in a potent dosedependent reduction of HuH7 xenografts in association with a significant decrease in Ki-67 and α-fetoprotein production, nuclear NF-κB content, polo-like kinase 1, Rb phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced apoptosis of HuH7 xenografts was associated with inhibited survivin phosphorylation. Silibinin-reduced growth of HuH7 xenografts was associated with decreased p-ERK, increased PTEN expression and the activity of silibinin was correlated with decreased p-Akt production, indicating involvement of PTEN/PI3K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin-reduced growth of HuH7 xenografts was also associated with a significant increase in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-1.CONCLUSION: Silibinin reduces HCC xenograft growth through the inhibition of cell proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing cell apoptosis, and increasing histone acetylation and SOD-1 expression.

8-硝基白杨素诱导HL-60细胞凋亡和抑制增殖与PTEN-Akt途径的相关性研究

目的观察8-硝基白杨素(NOChR)抑制人急性髓性白血病细胞系(HL-60)细胞增殖和诱导凋亡的作用,并探讨其作用机制。方法体外培养HL-60细胞;MTT比色法检测增殖活性;流式细胞术定量分析细胞凋亡程度;琼脂糖凝胶电泳观察DNA梯形条带。Western Blot分析HL-60细胞PTEN、P-Akt蛋白表达的影响。结果NOChR可显著抑制HL-60细胞增殖,呈浓度依赖性,IC50为1.34μmol;NOChR具有诱导HL-60细胞凋亡的作用,且呈浓度和时间依赖性。NOChR以浓度和时间依赖方式上调HL-60细胞PTEN蛋白的表达和抑制P-Akt蛋白的表达,其作用可被PPARγ特异性阻断剂GW9662(10μmol)预孵育拮抗。结论NOChR诱导HL-60细胞凋亡作用与其活化PPARγ、上调PTEN蛋白表达、抑制Akt磷酸化相关。

奥美拉唑逆转人肺腺癌耐顺铂细胞株A549/DDP耐药性的研究

目的:探讨液泡ATPase[vacuolar(H+)-ATPase,V-ATPase]非特异性抑制剂奥美拉唑(omeprazole,OME)逆转人肺腺癌耐药细胞株A549/DDP的耐药性及可能的作用机制。方法:以非细胞毒性浓度4μg/mL的OME预处理A549/DDP细胞24 h,再用2μg/mL顺铂(cisplatin,DDP)处理A549/DDP细胞。MTT法检测细胞的增殖抑制率,激光扫描共聚焦显微镜(laser scanning confocal microscope,LSCM)法间接检测细胞内pH值的变化,FCM法检测凋亡相关蛋白Bcl-2和PTEN的表达,RT-PCR法检测VATPase、Bcl-2和PTEN mRNA的表达。结果:OME具有逆转A549/DDP细胞耐药性的作用,逆转倍数为1.45(P<0.01);OME预处理后A549/DDP细胞内pH值明显降低,Bcl-2蛋白表达下降,PTEN蛋白表达增加(P<0.01)。V-ATPase在亲本A549及A549/DDP细胞中相对表达量分别为0.88±0.00和0.99±0.00(P<0.01);A549/DDP细胞中V-ATPase在有无OME预处理的情况下的相对表达量分别为1.09±0.00和1.05±0.02,差异无统计学意义。Bcl-2 mRNA相对表达量下降(P<0.01),PTEN mRNA相对表达量增加(P<0.01)。结论:V-ATPase在A549/DDP细胞中高表达,OME能部分逆转A549/DDP耐药性,其作用机制可能与上调PTEN和下调Bcl-2表达有关。