川芎嗪对小鼠肺癌血管生长和VEGF表达的抑制

目的　观察川芎嗪对实体肿瘤及其血管生长的抑制作用及作用环节。方法　用C57BL小鼠接种Lewis肺癌细胞造模 ,川芎嗪注射液 5 0、10 0、2 0 0mg·kg-1·d-1腹腔注射2 1d后 ,检测肿瘤体积、重量、肺转移灶数及微血管密度 ,并用WesternBlot法和免疫组化法分析肿瘤细胞VEGF的表达。结果　川芎嗪能减少小鼠Lewis肺癌肿瘤体积、重量和肺转移灶数 ,并能降低肿瘤微血管密度 ,抑制肿瘤细胞VEGF的表达。结论　川芎嗪能抑制小鼠Lewis肺癌的生长与转移 ,其机制可能与抑制VEGF表达 ,降低肿瘤微血管密度有关。     

人参皂苷Rh2 对荷Lewis 肺癌小鼠抗肿瘤作用

目的观察人参皂苷Rh2（ginsenoside Rh2,G-Rh2）对荷Lewis肺癌小鼠抗肿瘤作用并探讨其作用机制。方法建立Lewis肺癌实体瘤模型,观察G-Rh2的抗肿瘤作用、观察肿瘤内血管密度（MVD）,以及免疫组化法观察瘤体血管内皮生长因子（VEGF）的表达。结果 0.3 mg·kg^-1、1.0 mg·kg^-1和3.0 mg·kg^-1G-Rh2组对Lewis肺癌小鼠实体瘤均有抑制作用（P〈0.05）;1.0 mg·kg^-1和3.0 mg·kg^-1 G-Rh2组MVD明显低于对照组（P〈0.05）;免疫组化结果显示,0.3 mg·kg^-1、1.0 mg·kg^-1和3.0 mg·kg^-1 G-Rh2组瘤组织内的VEGF蛋白表达阳性率均低予对照组（P〈0.05）。结论 G-Rh2可抑制Lewis肺癌生长及抑制肿瘤新生血管生成的作用,可能是通过降低VEGF表达来实现的。     

苦参碱对C57BL/6J小鼠Lewis肺癌VEGF表达的影响

目的 研究苦参碱对小鼠Lewis肺癌的作用,并探讨其作用机制.方法 建立小鼠Lewis肺癌模型,将实验小鼠分为生理盐水组、不同剂量苦参碱组、环磷酰胺组,计算原发瘤抑制率及微血管密度;采用RT-PCR和Western blot法检测原发瘤组织VEGF mRNA和蛋白表达.结果 应用苦参碱各剂量组,小鼠原发瘤抑制率、微血管...     

威麦宁抑制小鼠Lewis肺癌移植瘤的生长及其血管生成的实验研究

目的:探讨威麦宁对小鼠Lewis肺癌移植瘤生长及其血管生成作用的影响。方法:建立小鼠Lewis肺癌移植瘤模型,用药后取瘤组织称重并计算抑瘤率;瘤组织切片HE染色,光镜下进行形态学观察;免疫组化法检测瘤组织血管内皮细胞CD34的表达情况并计数微血管密度(MVD)。结果:威麦宁浓度在100mg/kg.d、250mg/kg.d时,对小鼠Lewis肺癌的抑制率分别为19.14%和51.56%;对照组癌巢间微血管丰富,用药组瘤组织及其周围微血管均减少;用药组瘤组织内MVD明显低于NS组(P<0.01)。结论:威麦宁能减少肿瘤组织血管生成,从而抑制小鼠移植瘤的体内生长。     

低氘水对Lewis肺癌模型小鼠血管内皮生长因子表达的影响

目的研究低氘水(deuterium depleted water,DDW)对Lewis肺癌模型小鼠的抑瘤作用及小鼠肿瘤组织血管内皮生长因子(VEGF)表达的影响。方法将Balb/c小鼠随机分为模型组(蒸馏水)、正常组、阳性对照组(顺铂)和体积分数分别为0.005 0%,0.007 5%和0.010 0%的低氘水组(DDW),每组10只。比较各组小鼠的行为、抑瘤率、脾脏系数、胸腺系数、病理学检查、相关生化指标测定及肿瘤组织中血管内皮生长因子(VEGF)的表达。结果模型组小鼠活动度减少,精神差、皮毛缺少光泽,喜扎堆,出现饲料消耗量减少及毛发脱落等状态。阳性对照组活动度较模型组增加,低氘水组与模型组比较,活动度优于模型组,毛发脱落现象少,少有扎堆现象。阳性对照组、体积分数为0.005 0%DDW组、体积分数为0.007 5%DDW组以及体积分数为0.010 0%DDW组的抑瘤率分别为45.32%,36.66%,16.74%和9.44%。与模型组和阳性对照组比较,血清肿瘤四项特异性生化指标差异均具有统计学意义。各给药组小鼠的脾脏系数、胸腺系数及VEGF的表达均明显降低,差异有显著统计学意义(P<0.01)。结论低氘水对肺癌模型小鼠有一定抑瘤作用,作用机制可能与抑制血管内皮生长因子VEGF的表达有关。     

二味康口服液对小鼠Lewis肺癌的抗癌作用

探讨二味康口服液的抗癌作用。方法：用Ｌｅｗｉｓ肺癌小鼠模型,观察二味康抗癌作用。结果：二味康口服液预防和治疗给药均能延长Ｌｅｗｉｓ肺癌小鼠平均生存时间;对小鼠Ｌｅｗｉｓ肺癌瘤重增长及自发肺转移有明显抑制作用。结论：二味康口服液有明显的抗癌作用,与环磷酰胺合用作用可见增强。     

丹参联合放疗抑制小鼠肺癌肿瘤血管生成的实验研究

目的探讨丹参联合放疗对小鼠Lewis肺癌肿瘤组织中微血管密度(MVD)的影响。方法建立Lewis肺癌荷瘤鼠模型后,随机分为模型组、丹参低剂量组(丹低组)、丹参高剂量组(丹高组)、放疗组、丹低+放疗组(联合1组)、丹高+放疗组(联合2组),每组各10只小鼠。各组于接种第二日起每天腹腔注射给药,连续12 d,放疗组、联合1组、联合2组于接种第7日起给予钴-60照射肿瘤局部,放疗剂量2 Gy.d-1,连续5 d。末次给药24 h后处死小鼠,剥离肿瘤组织称重,计算抑瘤率;免疫组化法检测肿瘤组织中微血管密度(MVD)。结果丹参低剂量联合放疗组的微血管密度较放疗组和丹参低剂量组明显降低(P<0.05)。结论丹参联合放疗对Lewis肺癌小鼠肿瘤血管生成有明显的抑制作用。     

促血管生成素-2（Ang-2）在非小细胞肺癌（NSCLC）中的表达与肿瘤血管生成的关系

目的检测促血管生成素-2（Ang-2）在非小细胞肺癌（NSCLC）中的表达，研究它与血管内皮生长因子（VEGF）表达及微血管密度（MVD）的关系，探讨其在非小细胞肺癌血管生成中的作用。方法用免疫组化法检测37例非小细胞肺癌组织及15例癌旁正常组织中Ang-2、VEGF及CD34相关抗原的蛋白表达情况，分析各个指标在各组表达的差异，研究各个指标的相互关系。结果非小细胞肺癌组织中Ang-2表达阳性率、VEGF记分和微血管密度计数（MVD）均明显高于癌旁正常组织；Ang-2表达与VEGF和MVD表达有明显相关性（r分别0．509和0．615，P〈0．05）；非小细胞肺癌中Ang-2表达阳性者与Ang-2表达阴性者相比，VEGF记分和MVD显著不同（P〈0．05）；Ang-2表达与非小细胞肺癌的淋巴结转移及肿瘤的分级有关（P〈0．05）。结论Ang-2与非小细胞肺癌的浸润、进展密切相关；其对非小细胞肺癌肿瘤血管生成有促进作用，这种作用具有明显的VEGF依赖性。     

小鼠Lewis肺癌胸腔移植模型的建立和应用

目的探讨肺癌动物模型的建立及其对药物治疗的反应。方法 160只C57BL/6小鼠随机分为胸腔移植组和皮下移植组,每组80只。在小鼠腋后线第6肋间胸腔或小鼠腋部皮下,分别移植鼠源性Lewis肺癌细胞0.2ml(5×106/ml)。采用不同化疗药物治疗后,观察小鼠生存状态,用免疫组化方法检测肿瘤组织内增殖细胞核抗原(PCNA)和血管内皮生长因子(VEGF)蛋白表达。结果与皮下移植组比较,胸腔移植组小鼠治疗后生活状态好转,VEGF表达和PCNA阳性细胞数明显下降。结论与小鼠皮下移植肺癌模型比较,胸腔移植模型能更好的反映药物的作用。     

绞股蓝总皂甙对Lewis肺癌荷瘤小鼠肿瘤生长及免疫功能的影响

观察绞股蓝总皂甙对Ｌｅｗｉｓ肺癌荷瘤小鼠肿瘤生长,脾淋巴细胞数及ＮＫ活性的影响。方法整体动物的抑瘤试验,脾淋巴细胞计数及ＮＫ活性测定。结果：ＧＰｓ对荷瘤小鼠Ｌｅｗｉｓ肺癌细胞具有明显的抑制作用,在剂量１０、２０、４０ｍｇ／ｋｇ腹腔注射给药条件下,其抑瘤率分别为（３０．７±１．２）％,（５１．５±２．５）％（Ｐ〈０．０１）。同时,ＧＰｓｉｐ给药后荷瘤小鼠脾淋巴细胞总数明显增加,外周血淋巴细胞ＮＫ活性     

The effect of topiramate on tumor-related angiogenesis and on the serum proteome of mice bearing Lewis lung carcinoma

Topiramate has been used in patients with brain tumors who develop epilepsy. In our previous research we found topiramate could inhibit tumor metastases of Lewis lung carcinoma in C57BL/6 mice. In this study we aimed to assess the antimetastatic activity of topiramate and determine its mechanism of action. After confirming the effects of topiramate on Lewis lung carcinoma in C57BL/6 mice, we assessed the mRNA expression of carbonic anhydrases II and IX, and the vascular endothelial growth factor (VEGF) distribution in tumor tissue. We studied the role of topiramate on primary angiogenesis using a chicken embryo chorioallantoic membrane angiogenesis model, and analyzed the protein profile of serum from mice treated with or without topiramate by two-dimensional electrophoresis. We found that topiramate significantly reduced the primary tumor growth (P<0.05) and the degree of damage to the lung alveoli caused by metastatic tumor deposits. The two-dimensional electrophoresis revealed changes that occurred with topiramate treatment and four down-regulated protein spots were clearly identified as tropomyosin, osteopontin, transthyretin, and serum amyloid A-1. The mRNA and protein expression of serum amyloid A-1, osteopontin and its receptor, integrin α(v)β(3) in tumor tissue were reconfirmed. The results suggest that topiramate has antitumor and antimetastatic effects on Lewis lung carcinoma. Its mechanism of action may be related to its inhibition of angiogenesis by down-regulation of osteopontin, VEGF and carbonic anhydrase II.     

乙酰唑胺抑制肿瘤转移及荷瘤小鼠肺相关蛋白质的表达

目的:研究乙酰唑胺对肿瘤转移的抑制及相关蛋白质的表达.方法:以 Lewis肺癌为肿瘤转移模型,观察乙酰唑胺对肿瘤转移的影响;用SDS/PAGE、 Western blot、IEF和肽质量指纹谱的方法观察相关蛋白质的变化.结果:乙酰唑胺可以显著抑制肿瘤转移,肺转移抑制率为83.9％.荷瘤小鼠肺组织中水通道蛋白-1和肌动蛋白表达明显增高,用乙酰唑胺治疗后水通道蛋白-1表达降低.结论:乙酰唑胺具有抗肿瘤转移作用,其机制可能与抑制水通道蛋白-1的表达有关;水通道蛋白-1和肌动蛋白可望成为肿瘤肺转移诊疗的新靶标.     

Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma

Phyllanthus urinaria, a widely used herb medicine in Asia, was tested for its anti-tumor effect in vivo for the first time. The anti-tumor activity in P. urinaria extract was evaluated by its effect on tumor developed in C57BL/6J mice with implantation of Lewis lung carcinoma cells. The oral administration of P. urinaria to mice caused significant inhibition of tumor development with lower occurrence rate and markedly reduced tumor size. Neither the total body weight of mouse nor the weights of organs including heart, lung, liver, spleen and kidney revealed any difference between two groups, suggesting limited in vivo cytotoxic effect of P. urinaria in mice. TUNEL assay demonstrated the increase of apoptosis in tumor sections prepared from P. urinaria-treated mice compared with control mice. It is worth of note that the neovascularization in tumor was inhibited in P. urinaria-treated mice, which implicated the potential anti-angiogenic effect of P. urinaria. Further study using an in vitro matrix-induced tube formation of HUVECs again confirmed the anti-angiogenic action of P. urinaria. P. urinaria exerted no inhibitory effect on the growth of HUVECs, however, the migration of HUVECs as analyzed using transwell assay was suppressed markedly by P. urinaria in a dose-dependent manner. All together, the present study indicated that P. urinaria extract is an anti-tumor and anti-angiogenic agent, which can be used safely in animals.     

川芎嗪联合顺铂对Lewis小鼠肺腺癌移植瘤与血管生成的影响

目的研究川芎嗪联合顺铂对Lewis肺腺癌小鼠移植瘤生长及抑制血管生成的作用机制。方法培养Lewis小鼠肺腺癌细胞,建立移植瘤模型。按照体重将成功制备的荷瘤小鼠模型随机分成4组,每组15只:模型组、顺铂组、川芎嗪组、联合组。模型组:0.9% NaCl,顺铂组:2 mg·kg^-1,川芎嗪组:100mg·kg^-1,联合组:两种药物相加。均每次0.2 mL,干预2周。称量瘤重,计算抑瘤率;用免疫组化方法检测每组血管内皮生长因子(VEGF)、血管抑制蛋白(VASH-1)的表达。结果给药后,联合组、顺铂组、川芎嗪组的抑瘤率分别为54.81%,32.36%,18.36%,与模型组(抑瘤率为0)比较,差异均有统计学意义(均P<0.05)。联合组、顺铂组、川芎嗪、模型组的VEGF表达分别为20.37±2.02,28.07±4.29,26.43±4.69,62.14±6.78;这4组的VASH-1表达分别为9.04±1.01,10.10±1.61,11.53±1.96,12.94±1.10,3个给药组与模型组相比,差异均有统计学意义(均P<0.05)。Pearson相关性分析:VEGF与VASH-1成正相关(r=0.664,P<0.05)。结论川芎嗪联合顺铂协同抑制Lewis小鼠移植瘤生长,其作用机制可能为川芎嗪与顺铂可以直接作用癌细胞,同时降低VEGF与VASH-1表达,发挥抗血管生成作用。     

川芎嗪联合顺铂对小鼠肿瘤血管生成的研究

目的研究川芎嗪联合顺铂对小鼠Lewis肺癌血管内皮生长因子(VEGF)和半乳糖凝集素1(Galectin-1)表达的影响。方法建立小鼠Lewis肺腺癌移植瘤模型。按照体重将小鼠随机分为4组,每组10只:空白组(0.9%NaCl 0.2mL),川芎嗪组(100 mg·kg^-1,0.2 mL),顺铂组(2 mg·kg^-1,0.2 mL),联合组(川芎嗪+顺铂,剂量同上,0.2 mL),腹腔注射,每日1次,给药14 d后,处死小鼠,计算抑瘤率。用免疫组化法检测VEGF、Galectin-1的表达。结果川芎嗪组、顺铂组、联合组的抑瘤率分别为20.42%,34.65%,59.81%。VEGF和Galectin-1的表达:空白组、川芎嗪组、顺铂组、联合组分别为(62.41±8.83)×10~3,(27.84±2.25)×10~3,(28.67±2.33)×10~3,(23.52±2.76)×10~3;(25.96±3.50)×10~3,(20.29±2.85)×10~3,(19.11±2.42)×10~3,(15.15±2.43)×10~3。与空白组比较,3个给药组差异均有统计学意义(均P<0.01);与川芎嗪组和顺铂组比较,联合组差异均有统计学意义(P<0.05,P<0.01)。VEGF与Galectin-1的表达呈正相关性(r=0.638,P<0.05)。结论川芎嗪能够抑制Lewis肺癌移植瘤生长,与顺铂联用有协同抑制作用,其作用机制可能是通过抑制VEGF与Galectin-1表达来抑制肿瘤血管生成进而抑制肿瘤生长。     

Responses to endotoxin of mice bearing the Lewis lung (3LL) carcinoma

We examined factors which could be responsible for altered sensitivity to endotoxin in tumor bearing mice in order to gain a greater insight into the mechanisms responsible for the toxic effects of the substance. C57BL/6 mice engrafted with 2 × 10⁵ Lewis lung carcinoma cells were injected with 300 μg Salmonella typhosa endotoxin 3,7 and 14 days after tumor cell implantation. A biphasic pattern of mortality was noted when 23 of 35, 1 of 20, and 33 of 34 mice died within 48 hr of injection with endotoxin on days 3, 7 and 14, respectively. Only 1 of 30 normal mice died after injection with this dose of endotoxin. Intestinal penetration by microbial substances did not explain the biphasic sensitivity to endotoxin. Sensitivity to endotoxin seen at day 14 could be associated with tumour mass, but this association would not explain sensitivity to endotoxin at day 3. Regression of tumour growth and decreased tumor-induced mortality was observed in mice injected with 300 μg of endotoxin 7 days after tumor implantation. Larger doses of endotoxin (400–700 μg) had a better therapeutic value but at the expense of increased endotoxin-induced mortality.     

Increased susceptibility to the anticoagulant effect of warfarin in mice bearing the Lewis lung carcinoma. Role of vitamin K deficiency

This study reports an increased susceptibility to warfarin anticoagulation in mice bearing an experimental tumour, the Lewis lung carcinoma. In these animals, following a single i.v. injection of warfarin, the prothrombin complex activity decreased normally but recovered far slower than in controls, while the rate of degradation of the clotting factors was not modified. At the level of the vitamin K-dependent liver carboxylase, it was possible to demonstrate an increase in the endogenous substrate (reflecting an impairment of the carboxylase vitamin K dependent system). This abnormality was reversed by vitamin K administration and can be reasonably ascribed to a vitamin K deficiency in association with tumour growth.     

二味康口服液对荷瘤小鼠免疫功能的影响

探讨二味康口服液抗癌及免疫调节机理。方法：采用二味康口服液不同剂量对荷Lewis肺癌小鼠进行实验。结果：二味康口服液治疗给药可使荷瘤小鼠低下的T、B淋巴细胞增殖反应,脾细胞产生IgM,血清中IgG含量及脾细胞产生IL-2恢复至接近正常水平,并促进荷瘤小鼠腹腔巨噬细胞产生IL-1和TNF。结论：二味康口服液属中药BRM（生物反应调节剂）范畴,其抗癌作用与其增强免疫功能有关。     

丹参联合放疗对小鼠Lewis肺癌肿瘤组织微血管的影响

目的探讨丹参联合放疗对小鼠Lewis肺癌肿瘤组织微血管密度(MVD)的影响。方法建立Lewis肺癌荷瘤鼠模型后,60只荷瘤鼠随机均分为模型组、丹参组(低、高剂量)、放疗组、丹参低剂量+放疗组(联合1组)、丹参高剂量+放疗组(联合2组)。各组于接种第二日起每天ip给药,连续12 d,放疗组及联合1、2组于接种第7日起给予钴-60照射肿瘤局部,剂量2 Gy·d-1,连续5 d。末次给药24 h后处死动物,剥离肿瘤组织称重,计算抑瘤率;免疫组化法检测肿瘤组织MVD。结果联合1组的MVD较放疗组和丹参低剂量组明显降低(P<0.05)。结论丹参联合放疗对Lewis肺癌小鼠肿瘤血管的生成有明显的抑制作用。