赖氨匹林对B16黑色素瘤的增殖抑制及促凋亡作用

目的探讨赖氨匹林(aspisol)在体外和体内对小鼠B16黑色素瘤细胞的增殖抑制和诱导凋亡作用。方法利用MTT法和流式细胞术检测赖氨匹林对B16细胞的增殖抑制和诱导凋亡作用。用细胞悬液法将B16黑色素瘤细胞接种于小鼠前肢腋窝皮下,制备可移植肿瘤模型。次日给予不同浓度的赖氨匹林腹腔注射,每天1次,共28天,用达卡巴嗪(dacarbazine,DTIC)和生理盐水分别作阳性对照和阴性对照。计算aspisol的抑瘤率;原位凋亡检测法(TUNEL)检测赖氨匹林对肿瘤细胞凋亡的影响;免疫组化法检测aspisol对小鼠肿瘤组织的Survivin、C-erbB-2表达的影响。结果Aspisol可抑制B16细胞增殖,最大抑制率为(68.78±1.27)%,诱导B16细胞凋亡,最大凋亡率为15.8%。200、400、800mg·kg-1aspisol对小鼠黑色素瘤的抑瘤率分别为15.0%、32.3%、49.4%,40mg·kg-1DTIC的抑瘤率为51.4%。各给药组肿瘤细胞均呈现明显凋亡形态改变,不同浓度aspisol均明显下调小鼠肿瘤组织的Survivin、C-erbB-2表达。结论Aspisol在体外和体内能够抑制小鼠B16黑色素瘤增殖和诱导凋亡,其机制可能与抑制Survivin、C-erbB-2表达有关。     

赖氨匹林退热疗效观察

发热是呼吸系统最常见的临床表现,持续发热可引起体内调节功能紊乱等一系列不良反应,因此,对发热病人应采取积极降温措施。目前呼吸科降温以口服及肌注的方式,常用药物为扑热息痛、安乃近、安痛定,降温效果不太理想。注射用赖氨匹林可供口服、肌注及静注,具有起效快,血药浓度高,毒副作用小等优点。我院于98年～99年对50例发热病     

赖氨匹林退热疗效观察

高热是小儿急性感染常见的症状,需要及时作退热处理。目前大多用安痛定肌内注射,退热效果尚不满意。经用肌注赖氨匹林和安痛定的退热效果进行对照观察,结果表明,前者明显优于后者。     

赖氨匹林对儿科解热作用的临床观察

高热是小儿急性感染常见的临床表现 ,持续高热引起体内调节功能紊乱等一系列不良反应 ,因此对小儿高热应采取积极的降温措施。常用的儿科降温以滴鼻、口服及肌注方法 ,赖氨匹林可肌注及静注 ,具有起效快 ,血药浓度高 ,毒副作用小等优点。本组对小儿高热应用赖氨匹林静脉注射治疗 ,疗效显著 ,现报告如下 :1　资料与方法1 1　资料　选 2 0 0 2年 1月～ 2 0 0 3年 1月来我院儿科住院6 0 0例患儿 ,按随机原则分为两组 ,治疗组 2 94例 ,男 15 6例 ,女 138例 ,对照组 30 6例 ,男 186例 ,女 12 0例。两组年龄均在 6月～ 3岁 ,体温 >38 5℃ (腋温 )…     

赖氨匹林对高温患儿退热作用的观察

赖氨匹林是阿斯匹林和赖氨酸的复盐,可静脉或肌肉注射。高温患儿用药后15分钟、30分钟、60分钟、120分钟分别测体温,观察静注组无论在降温速度还是幅度上均明显大于肌注组,优于安痛定组。肌注组与安痛定组比较,二者起效时间相似,但以后作用大于安痛定组。表明赖氨匹林见效快,疗效显著,可直接静注,尤其适合需静脉点滴的高温患儿。     

赖氨匹林对肾绞痛的镇痛作用

目的：观察赖氨匹林对肾绞痛的镇痛效果。方法：１５６例肾绞痛病人（男性１１４例，女性４２例，年龄３６±ｓ９ａ），当肾绞痛发作时ｉｍ赖氨匹林０．９ｇ，３０ｍｉｎ后可再ｉｍ０．９ｇ，直至疼痛缓解。１ｄ最大用药量３．６ｇ。结果：显效８２例，有效６２例，无效１２例，镇痛总有效率为９２．３％。结论：赖氨匹林对肾绞痛有镇痛作用。     

赖氨匹林的细菌内毒素测定的方法学研究

目的建立赖氨匹林的细菌内毒素检查方法。方法采用《中国药典》2010年版细菌内毒素检查法中的凝胶法。结果 3批赖氨匹林中含内毒素的量均小于0.15EU。结论赖氨匹林可用细菌内毒素检查法进行安全性质量检查。     

赖氨匹林注射液不良反应分析

目的:为临床安全合理应用赖氨匹林提供参考。方法:检索1994年1月～2007年3月的《中国医院数字图书馆》国内公开发行的各种医药学期刊,对文献报道赖氨匹林出现的不良反应进行汇总分析。结果:赖氨匹林不良反应发生较为迅速,常在注射后数分钟内发生。结论:医师应询问患者的过敏史,注意合理的给药方法和用量。     

赖氨匹林对人宫颈癌HeLa细胞的抑制作用及其机制研究

目的探讨ERK1/2信号通路在赖氨匹林(aspisol)对人宫颈癌HeLa细胞抑制中的作用。方法分别采用MTT比色法、标准细胞集落形成分析法和Annexin V/PI双染法分析不同浓度aspisol(1、5、10mmol·L-1)对HeLa细胞增殖、细胞集落形成及细胞凋亡的影响;Western blot方法检测细胞外信号调节蛋白激酶(ERK1/2)/磷酸化(P-ERK1/2)和COX-2的表达。结果 aspisol(1、5、10mmol·L-1)可呈浓度依赖性抑制HeLa细胞的生长、降低克隆形成数量、诱导HeLa细胞的早期凋亡率、下调P-ERK1/2及COX-2的表达水平(P<0.01),但不影响总ERK表达(P>0.05)。结论 aspisol对宫颈癌HeLa细胞有抑制增殖、诱导凋亡的作用,其作用机制可能与抑制ERK1/2的活化进而下调COX-2的表达有关。     

赖氨匹林治疗肾绞痛156例报告

对156例肾绞痛患者应用赖氨匹林治疗,疼痛缓解率达(144/156)92.3%.该药用于治疗肾鲛痛具有起效快,镇痛时间长,毒副作用小,可重复用药,完成瘾性,适用人群广等特点.认为氨匹林可作为一种较好的治疗肾绞痛的首选药物.对该药治疗肾绞痛的机理进行了讨论.     

In vitro antiproliferative effect of a water-soluble Laminaria japonica polysaccharide on human melanoma cell line A375

A water-soluble polysaccharide WPS-2-1, purified from Laminaria japonica, has been found to have antitumor activity. In this study, WPS-2-1 exhibited high anti-proliferative activity on A375 cells in a dosedependent manner. Further investigation indicated that WPS-2-1 induced A375 cells apoptosis. Moreover, WPS-2-1-induced apoptosis was associated with the alteration in expressions of Bcl-2 family proteins. Mitochonadrial apoptotic pathway was involved in WPS-2-1-induced apoptosis, which included the loss of mitochondrial membrane and activation of caspase-3/9. The results in this study suggested that WPS-2-1 could effectively inhibit proliferation of A375 cells in vitro and induce apoptosis via mitochondrial apoptotic pathway. It might serve as a potential antitumor agent.     

Pseudolaric acid B induces apoptosis through p53 and bax/ Bcl-2 pathways in human melanoma a375-s2 cells

Pseudolaric acid B is a major compound found in the bark of Pseudolarix kaempferi Gordon. In our study, pseudolaric acid B inhibited growth of human melanoma cells, A375-S2 in a time- and dose-dependent manner. A375-S2 cells treated with pseudolaric acid B showed typical characteristics of apoptosis including morphologic changes, DNA fragmentation, sub-diploid peak in flow cytometry, cleavage of poly-ADP ribose polymerase (PARP) and degradation of inhibitor of caspase-activated DNase (ICAD). P53 protein expression was upregulated while cells were arrested at the G2/M phase of the cell cycle. There was a decrease in the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins, whereas pro-apoptotic Bax was increased. The two classical caspase substrates, PARP and ICAD, were both decreased in a time-dependent manner, indicating the activation of downstream caspases.     

Nitric oxide induces apoptosis and autophagy; autophagy down-regulates NO synthesis in physalin A-treated A375-S2 human melanoma cells

Physalin A is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has been used for the treatment of sore throat, hepatitis, eczema and tumors in China. Our previous study demonstrated that physalin A induced apoptosis and cyto-protective autophagy in A375-S2 human melanoma cells. Induction of reactive oxygen species (ROS) with physalin A triggered apoptosis. In this study, NO generated by physalin A induced apoptosis and autophagy in A375-S2 cells, since physalin A induced the expression of inducible nitric oxide synthase (iNOS) in the cells. Generation of NO partially promoted both apoptosis and autophagy in A375-S2 cells. NO suppressed mTOR expression, which led to autophagy induction. An autophagic inhibitor, 3-methyladenine (3MA) promoted NO production, while acceleration of autophagy with an autophagic agonist rapamycin repressed NO production, suggesting that autophagy and NO production form a negative feedback loop that eventually protects the cells from apoptosis. The results together with the previous study indicate apoptosis and autophagy induced by physalin A in A375-S2 cells; the autophagy, repressing production of reactive nitrogen species (RNS) and ROS, protects the cells from apoptosis.     

赖氨匹林与卡氮芥协同抗肿瘤作用的研究应用

目的 探讨赖氨匹林与卡氮芥协同抗肿瘤的作用价值.方法 通过基础实验、动物实验与临床观察等三大部分对赖氨匹林与卡氮芥作用进行研究.结果 ①基础实验：赖氨匹林对C6细胞具有促凋亡和增殖抑制作用;②动物实验：赖氨匹林与卡氮芥联合使用对胶质瘤具有显著性治疗作用;③临床观察：脑胶质瘤术后36例患者随访18个月,赖氨匹林、卡氮芥联合组疗效明显优于无化疗组和卡氮芥组.结论 赖氨匹林＋卡氮芥对动物模型胶质瘤有显著治疗效果.收集脑胶质瘤术后患者,初步证实赖氨匹林的抗胶质瘤的作用和它在神经外科临床中的应用前景.     

驱虫斑鸠菊提取物抑制恶性黑色素瘤A375细胞增殖的研究

目的探讨驱虫斑鸠菊提取物对人恶性黑色素瘤A375细胞的增殖以及对其酪氨酸酶活性和黑色素含量的影响。方法四甲基噻唑氮蓝比色法测定对A375细胞抑制作用;显微法观察细胞形态;比色法测定酪氨酸酶活性和黑色素含量。结果在一定质量浓度范围(1～40mg.L-1)内随着驱虫斑鸠菊提取物质量浓度增加可抑制黑色素瘤细胞的增殖;驱虫斑鸠菊提取物质量浓度小于10mg.L-1,对酪氨酸酶活性和黑色素合成抑制有增加的趋势;大于20mg.L-1时,显示一定的细胞毒性作用。结论驱虫斑鸠菊提取物能显著抑制恶性黑色素瘤A375细胞的增殖,在一定质量浓度范围内(1～40mg.L-1)有浓度依赖关系(P<0.05)。     

青藤碱增强表柔比星对黑色素瘤细胞侵袭的抑制作用

目的初探青藤碱如何增强表柔比星对黑色素瘤细胞侵袭的抑制作用。方法应用Transwell方法检测不同处理因素对A375细胞侵袭的影响。处理因素分为4组,分别为:生理盐水组(对照),表柔比星处理组、青藤碱处理组和两种药物联合处理组。通过Western blot及Real-time PCR检测不同因素作用下侵袭相关蛋白的变化。结果 5μg/mL表柔比星、10μg/mL青藤碱以及两种药物联合处理组24 h后对A375细胞侵袭的抑制率分别为20.40%±4.63%、14.40%±2.67%和50.32%±3.02%。药物联用后对A375细胞侵袭的抑制作用显著高于各单药组,组间比较差异有统计学意义(P<0.05)。青藤碱可以增强表柔比星对侵袭相关蛋白MMP-2和MMP-9的抑制作用。结论低浓度青藤碱(10μg/mL)可以显著增强低浓度表柔比星(0.1×PPC)对黑色素瘤细胞A375细胞侵袭的抑制作用,青藤碱可以作为化疗过程中的辅助用药,起到优化治疗效果的作用。     

Icariside II potentiates paclitaxel-induced apoptosis in human melanoma A375 cells by inhibiting TLR4 signaling pathway

Combination therapy of paclitaxel (taxol) with natural anti-tumor agents that are capable of inhibiting survival signals may provide a rational molecular basis for novel chemotherapeutic strategies. Our previous study showed that icariside II (IS), derived from Herba Epimedii, inhibited the proliferation of melanoma cells in vivo and in vitro through the regulation of apoptosis. In this report, the combination effects of paclitaxel and IS were investigated in human melanoma A375 cells. As compared to the treatment with paclitaxel alone, the co-administration of IS and paclitaxel resulted in an enhancement of apoptosis as revealed by WST-8 and PI assays. Meanwhile, Western blot analysis showed that the co-administration of IS and paclitaxel resulted in increases of cleaved caspase-3, one of the terminal pro-apoptotic proteins. In melanoma, IL-8 and VEGF are positively correlated with disease stage and a high probability of progression. We demonstrated that treatment of A375 cells with IS in combination with paclitaxel resulted in a significant decrease in the production of IL-8 and VEGF, compared with paclitaxel alone. Recent studies suggest that TLR4–MyD88–ERK signaling may be a novel target for reversing chemoresistance to paclitaxel. Our flow cytometry and Western blot data showed that paclitaxel activated TLR4–MyD88–ERK signaling and that IS treatment could effectively inhibit this paclitaxel-induced activation of TLR4–MyD88–ERK signaling. In conclusion, this study demonstrated for the first time that IS could potentiate paclitaxel-induced apoptosis in melanoma cells. These effects were mediated, at least in part, by inhibiting the activation of the TLR4 signal transduction pathways. These findings support further preclinical evaluation of IS as a new potential anti-tumor agent.     

Mechanism of autophagy induction and role of autophagy in antagonizing mitomycin C-induced cell apoptosis in silibinin treated human melanoma A375-S2 cells

The aim of this study was to elucidate the molecular mechanisms mediating silibinin-induced autophagy in A375-S2 cells. In the present study it was found that silibinin-induced autophagy through increasing the conversion of LC3 I to LC3 II and up-regulating Beclin-1 expression, which was concomitant with p53 suppression and NF-κB activation. P53 inhibitor, pifithrin-α (PFT-α), increased autophagy and enhanced the expression of NF-κB. Moreover, inducing p53 accumulation with MG132 reduced autophagic ratio, and repressed the expression and activation of NF-κB expression. NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) suppressed autophagy. Autophagic specific inhibitor 3-methyladenine (3-MA) treatment reversed silibinin-induced p53 suppression as well as NF-κB activation, suggesting that there was a positive feedback loop between p53 inhibition-mediated NF-κB activation and autophagy. In addition, we also found that 3-MA efficiently abrogated silibinin's cyto-protective effect against mitomycin C-induced cell death, and reversed the suppressive efficacy of silibinin on p53 expression, suggesting that autophagy contributed to silibinin's cyto-protective effect against mitomycin C-induced cell death in A375-S2 cells.     

吴茱萸碱在诱导人黑色素瘤A375-S2细胞凋亡过程中对SIRT1和p53蛋白的影响

目的研究吴茱萸碱(evodiamine)在诱导A375-S2细胞凋亡过程中对SIRT1和p53蛋白表达的调控。方法电镜观察吴茱萸碱诱导细胞凋亡过程中细胞形态的变化。Western blot方法分析药物作用后对SIRT1蛋白和p53及其下游p21蛋白表达的影响。结果经15μmol.L-1吴茱萸碱处理24 h的A375-S2细胞表现出典型的凋亡特征,即细胞表面微绒毛消失、胞质空泡化、染色质浓集、边聚。在吴茱萸碱诱导A375-S2细胞凋亡过程中,SIRT1蛋白的表达下降,p53和p-p53的表达有所上升,其下游p21蛋白也被激活。结论在吴茱萸碱诱导的A375-S2细胞凋亡中,p53及其下游p21蛋白被活化,SIRT1蛋白表达被下调。     

防己诺林碱抑制黑色素瘤的增殖转移

目的观察防己诺林碱对黑色素瘤细胞生长转移的影响。方法通过MTT实验,观察不同浓度防己诺林碱对A375细胞增殖的影响;利用Transwell实验,检测不同浓度防己诺林碱对A375细胞转移功能的影响。通过Western blot和RT-PCR,检测防己诺林碱对A375生长转移相关蛋白的影响。结果防己诺林碱可以抑制黑色素瘤细胞A375的增殖转移。10、20、40μM/L防己诺林碱处理A375细胞后,对其增殖的抑制率分别为43.81%±1.53%、48.64%±4.65%、50.69%±4.99%。20、40μM/L防己诺林碱处理A375细胞作用24 h后,对其转移的抑制率分别为14.95%±4.31%、33.03%±5.46%。防己诺林碱显著抑制细胞周期蛋白D1(Cyclin D1)、CDK4、CDK6、基质金属蛋白酶-2(MMP2)的表达(P<0.05)。结论防己诺林碱能显著抑制A375细胞的增殖转移,可作为治疗黑色素瘤的潜在化疗药物进行深入研究。