替莫唑胺诱导人神经母细胞瘤SK-N-SH细胞中MGMT基因启动子区过甲基化与依立替康敏感性的关系研究

目的探讨替莫唑胺对人神经母细胞瘤SK-N-SH细胞中MGMT基因启动子区甲基化状态的影响,及该影响与细胞对依立替康敏感性的关系。方法体外培养神经母细胞瘤SK-N-SH细胞株作为对照组,采用替莫唑胺处理的细胞株作为实验组,比较两组细胞中MGMT基因启动子区甲基化状态,Real-time PCR检测两组细胞中MGMT基因的表达变化。用MTT法检测两组细胞对依立替康药物的敏感性。结果替莫唑胺处理组细胞MGMT基因的甲基化程度较对照组显著增加。实验组细胞MGMT基因的表达下调,与对照组比较存在显著差异,两者的表达量差异倍数均值为-3.25±0.71。依立替康对实验组细胞的IC50为2.5mg·L-1,对照组的IC50为5.7mg·L-1。结论替莫唑胺能够通过增加SK-N-SH细胞中MGMT编码基因上游启动子区的甲基化程度,从而下调MGMT编码基因的表达量,进而增加SK-N-SH细胞对依立替康的敏感性。     

恶性骨肿瘤化疗药物敏感性研究

目的：分析恶性骨肿瘤化疗药物敏感性和多药耐药物,为选择敏感的化疗药物,制定个体化疗方案提供依据。方法：取恶性骨肿瘤新鲜标本32例（骨肉瘤20例,其他12例）,运用流式细胞术、单克隆抗体技术和定量免疫荧光技术,检测MTX等化疗药物作用后的恶性骨肿瘤细胞凋亡情况及其多药耐药基因（MDR一蛋白P170的表达,分析其化疗敏感性和耐药性。结果：不同化疗药物作用后的骨肉瘤细胞调亡百分比分别为：MTX30．50±10．22％,ADM26．28±9．35％,MMC23．11±7．38％,VP－1618．17±6．14％,VCR4．44±2．55％,CTX1．22±0．59％。10例骨母细胞型骨肉瘤,IvITX作用后瘤细胞凋亡百分比为12．16－41．52％。P170蛋白表达较高的8例肉骨瘤,对MTX等化疗药物的敏感性均低于P170低表达者。结论：恶性骨肿瘤的化疗敏感性有很大个体差异,流式细胞术分析化疗药物作用后的恶性骨肿瘤细胞调亡,是一种简单、快速、灵敏的化疗药敏检测方法。P170蛋白表达的流式分析,可预测恶性骨肿瘤的耐药性和化疗敏感性。     

趋化因子受体CXCR4及其配体CXCL12在肝癌侵袭 转移中的作用及机制

目的 探讨趋化因子受体 CXCR4 及其配体 CXCL12（CXCL12/CXCR4）在原发性肝癌侵袭转移中的作用 及机制。方法 分别采用 Western blot、免疫组化和 Real-time PCR 等方法检测 60 例肝癌及对应癌旁组织标本中 CXCL12/CXCR4 蛋白及 mRNA 表达水平。常规培养 4 种肝癌细胞（Huh7、MHCC97h、HepG2、Hep3B）和正常肝细胞 （7702）,Real-time PCR 检测上述细胞中 CXCL12、CXCR4 mRNA 的表达,筛选合适的实验细胞。将 CXCR4 干扰质 粒（sh-CXCR4）和对应空载体（sh-control）分别转染至 MHCC97h 构建稳转细胞系。Transwell 侵袭实验、细胞划痕实 验、MTT 实验分别检测 2 组细胞的侵袭、迁移和增殖能力。取稳定表达的 sh-control 和 sh-CXCR4 MHCC97h 细胞, 接种至 6 只裸鼠皮下,观察瘤体生长情况。Western blot 检测 sh-control 和 sh-CXCR4 MHCC97h 细胞及对应裸鼠移 植瘤中血管内皮生长因子-C（VEGF-C）的表达,同时对转染 CXCR 过表达质粒的 MHCC97h 中 VEGF-C 的表达水平 进行检测。结果 （1）Western blot、免疫组化和 Real-time PCR 的结果均证实肝癌组织中 CXCL12/CXCR4 蛋白及 mRNA 表达水平均高于癌旁组织。（2）Huh7、MHCC97h、HepG2、Hep3B 细胞中 CXCL12/CXCR4 mRNA 表达水平均高 于 7702 细胞,选取 MHCC97h 为实验细胞。转染 sh-CXCR4 的 MHCC97h 细胞的侵袭、迁移和增殖能力均明显低于 sh-control 组,同时接种含 sh-CXCR4 的 MHCC97h 细胞的裸鼠移植瘤的生长速度也明显小于 sh-control 组。（3）体外 和体内实验均证实 sh-CXCR4 组的 VEGF-C 表达水平均低于 sh-control 组,而过表达 CXCR4 后,VEGF-C 的蛋白表 达明显上调。结论 CXCL12/CXCR4 在原发性癌组织和肝癌细胞中呈现高表达,CXCL12/CXCR4 可能通过调控 VEGF-C 蛋白表达从而抑制肝癌细胞的增殖、侵袭和转移。     

靶向调控AQP4对非小细胞肺癌细胞化疗敏感性的调控作用

摘要：目的 探讨靶向沉默水通道蛋白4（AQP4）基因对非小细胞肺癌细胞化疗敏感性影响,并研究其分子作用 机制。方法 实时荧光定量 PCR（qRT-PCR）和 Western blot 分别检测非小细胞肺癌 A549 细胞以及顺铂耐药菌株 A549/DDP中AQP4 mRNA和蛋白的表达。设计靶向AQP4的siRNA-1和siRNA-2,采用siRNA抑制A549/DDP细胞 中AQP4的表达,筛选出最优siRNA,将其转染A549/DDP细胞,设立siRNA-NC组和空白对照组。CCK-8法检测细胞 增殖能力并计算各组细胞的半数抑制浓度（IC50）;流式细胞术检测细胞凋亡。Western blot检测P53和Bcl-2蛋白的 表达。结果 AQP4 mRNA和蛋白在A549/DDP细胞中的表达水平显著高于A549细胞,AQP4表达沉默后A549/DDP 细胞增殖抑制,细胞凋亡增加,对顺铂的敏感性增加,凋亡相关蛋白P53表达增加,而Bcl-2蛋白表达降低。结论 通 过靶向调控AQP4的表达可以增加非小细胞肺癌细胞对化疗药物的敏感性。     

CXC趋化因子受体4及基质细胞衍生因子1在宫颈癌组织中的表达及其与化疗药物敏感性之间的关系

目的研究CXC趋化因子受体4(CXCR4)及基质细胞衍生因子1(SDF)-1在宫颈癌组织中的表达情况,及其与宫颈癌常规化疗药物敏感性之间的关系。方法收集山西医科大学第一医院2017年6月至2018年6月手术切除的宫颈癌组织新鲜标本40例,采用MTT法检测原代培养宫颈癌细胞对顺铂、环磷酰胺、紫杉醇、5-氟尿嘧啶的体外药物敏感性,蛋白印迹法检测癌组织中CXCR4及SDF-1的表达情况,分析CXCR4及SDF-1的表达与药物敏感性之间的关系。结果不同宫颈癌细胞体外对化疗药物敏感性存在差异,紫杉醇,顺铂,5-氟尿嘧啶及环磷酰胺的平均抑制率分别为:65±11、52±10、32±12、19±7,差异有统计学意义(P<0.05);与癌旁组织相比,CXCR4及SDF-1在宫颈癌组织中的表达显著增高(P<0.05),CXCR4及SDF-1的表达与肿瘤的分化程度及临床分期有关(P<0.05)。CXCR4及SDF-1在紫杉醇耐药组中的表达显著高于敏感组(P<0.05),SDF-1在顺铂耐药组中的表达显著高于敏感组(P<0.05)。结论 MTT药敏实验对宫颈癌化疗药物的选择具有一定的参考价值,CXCR4及SDF-1在宫颈癌中表达上调,可能与紫杉醇及顺铂的耐药有关。     

细胞信号转导抑制因子1沉默增强人口腔癌细胞对化疗药物的敏感性

目的 研究细胞因子信号转导抑制因子1(SOCS1)基因沉默对人口腔癌细胞化疗药物敏感性的影响及相关机制。方法 Western blotting及实时定量PCR验证SOCS1干扰序列沉默人口腔癌KB细胞株中SOCS1的表达水平;MTT法分析细胞对化疗药物敏感性的变化;流式细胞术检测细胞凋亡。结果 将SOCS1干扰片段转染KB细胞后,SOCS1 mRNA及蛋白表达水平均明显降低。沉默SOCS1表达后,化疗药物5-氟尿嘧啶和长春新碱对KB细胞的半数抑制浓度(IC50)均显著变小(P<0.05),SOCS1沉默还可增加长春新碱诱导的细胞凋亡(P<0.05),SOCS1表达抑制后KB细胞NF-κB和Caspase-3的蛋白表达水平明显降低,与对照组比较差异均有统计学意义(P<0.05);结论 SOCS1表达有效抑制后,人口腔癌细胞KB对化疗药物的敏感性增强,且促进化疗药物诱导的肿瘤细胞凋亡。     

环状RNA circNHSL1在小儿神经母细胞瘤中的表达及化疗耐受中的作用

目的：探讨环状RNA circNHSL1在小儿神经母细胞瘤中的表达及化疗耐受中的作用。方法：收集2016-2019年于我院就诊并接受手术联合阿霉素和顺铂化疗的神经母细胞瘤患儿60例，其中化疗敏感患儿35例，化疗耐受患儿25例。采用实时荧光定量聚合酶链式反应（qPCR）检测circNHSL1在神经母细胞瘤和化疗耐受患儿中的表达差异。构建人神经母细胞瘤细胞SH-SY5Y的阿霉素耐药株，检测阿霉素耐药细胞的circNHSL1表达量。通过沉默circNHSL1，采用细胞计数试剂盒（CCK-8）和流式细胞仪观察细胞增殖和凋亡情况。采用酶联免疫吸附试验（ELISA）和蛋白免疫印记法检测可能的转化生长因子-β（TGF-β）/Smad信号通路改变，并给予人重组TGF-β1进行回复实验，观察其在circNHSL1沉默细胞中的作用。结果：环状RNA circNHSL1在神经母细胞瘤中的表达高于正常组织（P<0.01），在化疗耐受患儿和耐药细胞株中的表达高于化疗敏感患儿（P<0.05）。在化疗耐受的细胞中，沉默circNHSL1细胞增殖活性降低，而凋亡率升高（P<0.01），TGFβ1分泌水平和表达量及其下游p-Smad2、p-Smad3表达量均降低（P<0.01）。再次给予人重组TGF-β1处理circNHSL1沉默的耐药细胞后，细胞增殖活性升高，而凋亡率降低，恢复耐药特性。结论：环状RNA circNHSL1在小儿神经母细胞瘤和化疗耐受组织中存在高表达现象，可通过激活TGF-β/Smad信号通路参与化疗耐受作用。     

开心散对Aβ25-35诱导损伤SH-N-K神经细胞的保护作用及机制

目的观察开心散对神经毒性物质β-淀粉样肽(Aβ25-35)诱导损伤的SK-N-SH细胞的保护作用。方法用Aβ25-35处理人神经母细胞瘤细胞(SK-N-SH细胞),模拟阿尔茨海默病(AD)病人脑内神经元病理损伤,并以含开心散(KXS)药物血清拮抗其作用。以MTT法测定细胞存活率,酶反应法检测细胞内超氧化物歧化酶SOD水平变化,流式细胞技术检测细胞凋亡率。逆转录聚合酶链式反应(RT-PCR)检测淀粉样肽蛋白前体(APP)基因、Aβ降解酶NEP基因的表达情况,Westernblots法检测APP蛋白表达。结果试验显示暴露Aβ25-35后培养SK-N-SH细胞存活率明显下降,凋亡细胞比例增加。而含开心散药物血清处理能显著提高Aβ25-35损伤细胞的存活率,减少细胞凋亡率,同时提高细胞内SOD的活力(P<0.01)。RT-PCR结果显示开心散可降低Aβ代谢相关的APP基因的表达并提高NEP基因的表达,APP蛋白表达显著减少。结论AD病理相关的Aβ25-35能造成神经元细胞损伤死亡,开心散对毒性Aβ25-35诱导的神经细胞损伤具有一定保护作用,其作用机制可能与开心散能增加抗氧化酶SOD活力,同时下调内源性APP基因表达,上调NEP基因表达,减少内源Aβ产生,从而抑制细胞死亡有关。     

干扰c-myc基因表达增强人胰腺癌细胞对吉西他滨和卡铂的敏感性

目的　探讨干扰c-myc 基因表达对人胰腺癌细胞SW1990 对化疗药物敏感性的影响。方法　采用实时定量PCR和Western blot 检测人胰腺癌细胞系SW1990 中c-myc 基因的干扰效果;MTT 法检测癌细胞对化疗药物吉西他滨和卡铂的敏感性;流式细胞术检测吉西他滨诱导的细胞凋亡情况。结果　c-myc siRNA 显著下调人胰腺癌SW1990 细胞中c-myc 基因的mRNA 和蛋白表达水平。干扰c-myc 表达后,化疗药物吉西他滨和卡铂对SW1990 细胞的半数抑制浓度（IC50）均显著减小（P<0.05）,吉西他滨诱导的SW1990 细胞凋亡率显著升高（P<0.05）。结论　干扰c-myc 表达可增强人胰腺癌细胞株SW1990 对化疗药物吉西他滨和卡铂的敏感性。     

智脑胶囊调控PI3K/AKT/GSK-3β信号通路诱导阿尔茨海默病模型细胞增殖的研究

目的:探讨智脑胶囊(Zhinao Capsule,ZNC)对阿尔茨海默病(Alzheimer's disease,AD)体外细胞模型增殖的影响及其作用机制。方法:采用全反式维甲酸(all trans retinoic acid,ATRA)+冈田酸(okadaic acid,OA)刺激人神经母细胞瘤细胞(human neuroblastoma cell,SK-N-SH)建立AD体外模型,CCK8法筛选ZNC含药血清最佳作用浓度和时间;流式细胞术、RT-qPCR和Western blot法检测最佳浓度ZNC含药血清作用最佳时间后,对SK-N-SH细胞周期、凋亡及PI3K、AKT、GSK-3β mRNA、总蛋白和磷酸化蛋白表达的影响。结果:ATRA＋OA刺激后,SK-N-SH细胞活力降低,细胞凋亡增加,p-PI3K、p-AKT和p-GSK-3β蛋白表达显著降低,GSK-3β mRNA和总蛋白表达明显升高;给予ZNC干预后,不仅可明显促进SK-N-SH细胞增殖,抑制其凋亡,还可显著升高p-PI3K、p-AKT和p-GSK-3β蛋白表达,降低GSK-3β mRNA和总蛋白表达。结论:智脑胶囊可促进AD模型细胞增殖,其机制可能与调控PI3K/AKT/GSK-3β信号通路有关。     

Taiwan cobra cardiotoxins induce apoptotic death of human neuroblastoma SK-N-SH cells mediated by reactive oxygen species generation and mitochondrial depolarization

Although Naja naja atra cardiotoxin 3 (CTX3) and cardiotoxin 4 (CTX4) showed different cytotoxicity toward human neuroblastoma SK-N-SH cells, the two toxins induced apoptotic death on SK-N-SH cells. The apoptosis signals of CTX3 and CTX3 included ROS generation, increase in mitochondrial permeability transition, cytochrome c release to the cytosol and activation of caspase-9 and -3. However, CTX3 quickly induced the effects with higher magnitude compared with CTX4. ROS production and subsequent apoptotic cell death in CTX-treated cells were partly blocked by the antioxidant 2,3-dihydroxybenzoic acid. Nevertheless, mitochondria alteration and cytosolic cytochrome c release were not significantly attenuated by the antioxidant. Cell death was not completely inhibited by caspase-3 inhibitor. Moreover, cyclosporine A, an inhibitor of mitochondrial permeability transition, slightly decreased CTX-induced ROS generation by approximately 15%. Taken together, our data indicate that N. naja atra CTXs induce ROS generation that is not wholly dependent on mitochondrial dysfunction, and that the cytotoxic potency of CTX3 and CTX4 on SK-N-SH cells is, at least in part, correlated with their capability in inducing ROS generation and mitochondrial alterations.     

Involvement of mitochondrial alteration and reactive oxygen species generation in Taiwan cobra cardiotoxin-induced apoptotic death of human neuroblastoma SK-N-SH cells

Naja naja atra cardiotoxin 3 (CTX3) induced apoptotic death on human neuroblastoma SK-N-SH cells. The apoptosis signals of CTX3 included reactive oxygen species (ROS) generation, disruption of mitochondrial membrane potential (DeltaPsim), cytochrome c release to the cytosol and activation of caspase-9 and -3. However, CTX3-induced increase in mitochondrial permeability transition was not initiated by proteins of the Bcl-2 family. The collapse of DeltaPsim, release of cytosolic cytochrome c, production of ROS and subsequent apoptotic cell death in CTX-treated cells could not be completely abolished by either N-acetylcysteine (ROS scavenger) or cyclosporin A (an inhibitor of mitochondrial permeability transition). Co-incubation with rotenone, an inhibitor of mitochondrial electron transport chain complexes I, resulted in partial inhibition of CTX3-induced ROS generation but not the loss of DeltaPsim. Obviously, the dissipation of DeltaPsim was not an upstream event for ROS generation or vice versa. Given that CTX3 was able to induce the leakage of isolated mitochondria, our data indicate that CTX3-induced apoptotic death of SK-N-SH cells is mediated through mitochondrial alteration and ROS generation.     

Extragranular storage of the neuron blocking agent meta-iodobenzylguanidine (MIBG) in human neuroblastoma cells

Human SK-N-SH neuroblastoma cells accumulate and store the adrenal imaging agent metaiodobenzylguanidine (MIBG) with minor involvement of specialized cytoplasmic storage granules (Smets LA et al., Active uptake and extravesicular storage of meta-iodo-benzylguanidine in human neuroblastoma SK-N-SH cells. Cancer Res 49: 2941-2944, 1989). In the present study the mechanism of extravesicular MIBG retention was investigated and compared with granular storage of MIBG and norepinephrine (NE) in PC-12 pheochromocytoma cells. SK-N-SH cells concentrated both MIBG and NE by neuron-specific Uptake-1 but long-term retention was only observed with MIBG. Retention of accumulated NE was, however, promoted by inhibition of intracellular catecholamine degradation with pyrogallol. Drug release by controlled cell permeabilization and by KCl-induced exocytosis indicated that MIBG was mainly stored as freely diffusible, cytoplasmic molecules. SK-N-SH cells were depleted from stored MIBG by the Uptake-1 inhibitor imipramine but poorly so by the granule-depleting drug reserpine. Conversely, PC-12 cells were depleted by reserpine but insensitive to imipramine. The data suggest that extravesicular retention of MIBG in SK-N-SH cells is not based on intracellular sequestration but is solely due to efficient re-uptake of accumulated drug after leaking from the cells. The accumulation of MIBG in SK-N-SH cells, reflecting "pure" Uptake-1, appears to be a powerful system for exploring various cellular and molecular aspects of catecholamine uptake.     

Methyl jasmonate downregulates expression of proliferating cell nuclear antigen and induces apoptosis in human neuroblastoma cell lines

Recent evidence indicates that methyl jasmonate, a plant stress hormone, exhibits anticancer activity on human cancer cells. Whether methyl jasmonate could inhibit the growth of human neuroblastoma cells still, however, remains largely unknown. In this study, administration of methyl jasmonate to cultured neuroblastoma cell lines, SK-N-SH and BE(2)-C, resulted in a decrease of cell viability in a dose-dependent and time-dependent manner as demonstrated by MTT colorimetry and colony formation assay. The results from RT-PCR indicated that the expression of proliferating cell nuclear antigen, but not of cyclin D1, was downregulated by methyl jasmonate. Accordingly, the cell cycle of methyl jasmonate-treated neuroblastoma cells was arrested at the G0/G1 phase. Moreover, incubation of SK-N-SH and BE(2)-C cells with methyl jasmonate resulted in characteristic changes of apoptosis, as demonstrated by acridine orange-ethidium bromide (AO/EB) staining, Hoechst 33258 staining and flow cytometry. Moreover, methyl jasmonate decreased the expression of the X-linked inhibitor of apoptosis protein and survivin, critical members of the inhibitors of apoptosis protein family, in neuroblastoma cells. These findings indicate that methyl jasmonate suppresses the growth of cultured human neuroblastoma cells associated with downregulation of proliferating cell nuclear antigen, and induces apoptosis accompanied by downregulation of the X-linked inhibitor of apoptosis protein and survivin, which lays the groundwork for further investigation into the mechanisms of methyl jasmonate-mediated anticancer activities.     

Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells

Myristicin, 1-allyl-3,4-methylenedioxy-5-methoxybenzene, is a naturally occurring alkenylbenzene compound found in the nutmeg. The present study was conducted to assess the cytotoxic and apoptotic effects of myristicin on the human neuroblastoma SK-N-SH cells. We found that a dose-dependent reduction in cell viability occurs at myristicin concentration > or =0.5 mM in SK-N-SH cells. Apoptotic cell death was confirmed using DNA fragmentation, terminal deoxyribonucelotidyl transferase-mediated dUTP nick end labeling and by 4,6-diamidino-2-phenylindole staining. Microscopy was used to observe apoptotic cell morphology. Western blotting was used to investigate the protein expression of known apoptotic mediators including cytochrome c, caspase-3, and PARP. The apoptosis triggered by myristicin was accompanied by an accumulation of cytochrome c and by the activation of caspase-3. The results obtained suggest that myristicin induces cytotoxicity in human neuroblastoma SK-N-SH cells by an apoptotic mechanism. This myristicin-induced apoptosis provides further insight of the molecular mechanisms of myristicin toxicity.     

氟丙胺磷对人成神经细胞瘤SK-N-SH细胞分化的毒性机制

目的研究诱发迟发性神经病的氟丙胺磷对人成神经细胞瘤SK-N-SH细胞分化的影响及其作用机理。方法MTT法测定细胞增殖,全反式维A酸诱导细胞分化,显微测量有机磷酸酯对细胞分化的影响,比色法测定NTE活力和Western印迹分析总的和磷酸化的神经纤丝重链蛋白以及肌动蛋白的表达。结果50μmol·L-1对氧磷和氟丙胺磷对细胞增殖没有影响;此浓度下对氧磷不抑制细胞的分化,而氟丙胺磷抑制细胞分化;氟丙胺磷抑制神经病靶标酯酶,而对氧磷对其不抑制;氟丙胺磷抑制总的和磷酸化的神经纤维丝重链蛋白的表达,而对氧磷对两种状态的神经纤维丝重链蛋白没有明显的作用。对氧磷和氟丙胺磷对肌动蛋白的表达都无影响。结论氟丙胺磷对人成神经细胞瘤细胞分化的抑制是通过对总的和磷酸化的神经纤维丝重链蛋白表达的抑制实现的,并伴随着神经病靶标酯酶的抑制。     

The cytostatic- and differentiation-inducing effects of cyclopentenyl cytosine on neuroblastoma cell lines

This paper describes the effects of cyclopentenyl cytosine (CPEC) on the proliferation and cell-cycle distribution of the SK-N-BE(2)c and SK-N-SH neuroblastoma cell lines, as well as their ability to recover from treatment with CPEC. The IC50 value of SK-N-BE(2)c for CPEC, determined after 48 hr was 80 nM. SK-N-BE(2)c cells showed a time- and concentration-dependent accumulation in the S-phase of the cell cycle after 2 and 3 days of incubation with 50-250 nM CPEC, followed by a G0/G1-phase arrest after 4 days. After incubation with 50 nM CPEC for 2 days, SK-N-BE(2)c cells fully recovered and resumed logarithmic proliferation. In contrast, a complete and persistent growth arrest occurred when SK-N-BE(2)c cells were incubated for 2 days with 100 or 250 nM CPEC. The IC50 value of SK-N-SH, determined after 48 hr, for CPEC was > or =1 microM. SK-N-SH cells incubated with 250 nM or 1 microM CPEC showed a time-dependent accumulation in the S-phase of the cell cycle, followed by an accumulation in the G0/G1-phase, which reached a maximum of 84.1% after 7 days of incubation with 1 microM CPEC. SK-N-SH cells did not resume proliferation after removal of the drug. In addition, CPEC strongly induced differentiation in SK-N-SH cells. After 48 hr incubation with 250 nM CPEC, 90% of the cell population was differentiated. Both neuronal type and Schwannian type cells were observed. We conclude that at very low concentrations, CPEC has profound cytostatic- and differentiation-inducing effects on the neuroblastoma cells studied.     

吡喃阿霉素与表阿霉素治疗非霍奇金淋巴瘤的对比观察

目的:以吡喃阿霉素(THP)和表阿霉素(EPI)为主的联合方案治疗非霍奇金淋巴瘤(NHL),并进行疗效及不良反应的对比观察.方法:用THP和EPI为主的CHOP方案分别治疗非霍奇金淋巴瘤各23例.结果:两组治疗有效率分别为73.9%,78.3%,无显著性差异(P＞0.05).不良反应(骨髓抑制、恶心呕吐、肝功异常及心脏毒性)两组间无显著性差异(P＞0.05),THP组脱发率低于EPI组(P＜0.01).结论:THP,EPI治疗非霍奇金淋巴瘤的疗效相似,但THP脱发率低于EPI.     

IGF-I receptor signaling pathway is involved in the neuroprotective effect of genistein in the neuroblastoma SK-N-SH cells

Genistein, an isoflavone naturally found in soy products, displays estrogenic properties. Our previous study clearly demonstrated that genistein can activate the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in human breast cancer MCF-7 cells. The present study aims to test the hypothesis that the IGF-I receptor signaling pathway is involved in the neuroprotective effects of genistein in neuroblastoma SK-N-SH cells. Our results revealed that pretreatment with genistein resulted in an enhancement in the survival of human neuroblastoma SK-N-SH cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. 6-OHDA arrested the cells at G(0)G(1) phase and prevented S phase entry. Genistein pretreatment could reverse the cytostatic effect of 6-OHDA on cell cycle. The decreased mitochondrial membrane potential induced by 6-OHDA could be also reversed by genistein pretreatment. These effects could be completely blocked by co-treatment with JB-1, which is the specific antagonist of the IGF-I receptor. Furthermore, genistein pretreatment restored the 6-OHDA-induced up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein expression. Genistein treatment alone could significantly increase the phosphorylation level of MEK and induce ERE luciferase activity. Co-treatment with IGF-I could enhance the effect of genistein on cell proliferation and MEK phosphorylation. This study provides the first evidence that genistein has neuroprotective effects against 6-OHDA-induced neurotoxicity in SK-N-SH cells and activation of the IGF-I receptor signaling pathway might be involved in actions of genistein.