Zoledronic acid induces cell-cycle prolongation in murine lung cancer cells by perturbing cyclin and Ras expression

Zoledronic acid (ZOL) was shown earlier to prolong survival in animal models of lung cancer. The aim of this study was to examine whether alteration of intracellular cyclins, cyclin-dependent kinases, cyclin-dependent kinase inhibitors, retinoblastoma, and Ras protein expression and E2F localization are among the possible antilung cancer mechanisms driven by ZOL. Furthermore, we used geranylgeraniol to test whether the mevalonate pathway is involved in the antitumor effects of ZOL against lung cancer. Line-1 cells, a murine lung adenocarcinoma cell line, were examined. ZOL significantly slowed the growth of these cells both in vitro and in vivo. The ZOL-treated cells typically arrested at the S/G2/M phase of the cell cycle, accompanied by increased intracellular levels of cyclin A, B1, and CDC2 and decreased levels of cyclin D, p21, p27, phosphorylated retinoblastoma, and Ras. In addition, ZOL affected the distribution of E2F. When geranylgeraniol was added to the ZOL-treated cells, either in vitro or in vivo, tumor growth, cell-cycle progression, the expression of certain cyclins, and cyclin-related regulatory proteins were partially returned to that of untreated controls. Therefore, ZOL elicits cell-cycle prolongation that seems to be associated with alterations in the levels of certain cyclins and cyclin-related regulatory proteins. Furthermore, the mevalonate pathway regulates ZOL-induced murine lung cancer inhibition both in vitro and in vivo.     

罗格列酮增强顺铂对肺腺癌裸鼠移植瘤生长的抑制作用

目的观察罗格列酮(ROZ)和顺铂(DDP)合用对人肺腺癌A549细胞裸小鼠移植瘤生长的抑制作用,并初步探讨其作用机制。方法采用A549细胞株建立人肺腺癌裸鼠模型,将28只成瘤雌裸小鼠随机分成7组:①对照组(生理盐水0.2ml);②DDP低剂量组(1mg.kg-1);③DDP高剂量组(4mg.kg-1);④ROZ低剂量组(10mg.kg-1);⑤ROZ高剂量组(30mg.kg-1);⑥DDP低剂量组+ROZ低剂量组;⑦DDP低剂量组+ROZ高剂量组,隔天腹腔注射给药,共8次。于最后一次给药后48h处死各组小鼠,收集瘤标本行光镜观察,免疫组化检测PPARγ、PTEN和pAkt蛋白表达情况。结果①各实验组肿瘤的生长明显受到抑制,瘤质量明显低于对照组(P<0.01)。低、高剂量ROZ联合用药组较低剂量顺铂组抑瘤作用明显增强(P<0.05),其瘤重抑制率分别为52.11%和83.8%。②免疫组化:低、高剂量罗格列酮组与对照组比较,PPARγ、PTEN的表达上调,而pAkt的表达呈现下调,差异具有显著性(P<0.05),联合用药组该调节作用进一步增强(P=0.00)。③不良反应:高剂量顺铂组出现不良反应,其余各组无明显不良反应。结论罗格列酮能够增强顺铂对人肺腺癌A549细胞裸鼠移植瘤生长的抑制作用,其作用机制可能与罗格列酮激活PPARγ,上调PTEN的表达和抑制pAkt的表达有关。     

非小细胞肺癌凋亡相关基因与神经内分泌分化表达的研究

目的:探讨非小细胞肺癌神经内分泌分化特征与细胞凋亡及凋亡相关基因Apaf-1和Caspase-3表达之间的关系。方法:对100例非小细胞肺癌手术标本应用TUNEL法检测细胞凋亡,免疫组织化学SP法检测癌组织中神经内分泌标志物神经特异性烯醇化酶、嗜铬素A、突触素及凋亡相关基因Apaf-1、Caspase-3蛋白的表达。结果:30例非小细胞肺癌具有神经内分泌分化特征,其平均凋亡指数及Apaf-1、Caspase-3蛋白表达均显著高于不伴神经内分泌分化者(P<0.05或P<0.01);Apaf-1和Caspase-3表达之间呈正相关(r=0.2877,P<0.01),两者与细胞凋亡之间亦呈正相关关系(r分别为0.3859和0.2316,均P<0.05)。腺癌和腺鳞癌组织的Apaf-1蛋白表达阳性率较高(P<0.01),Caspase-3蛋白表达阳性率在老年患者、中高分化癌和伴淋巴结转移者较高(P<0.05或P<0.01)。结论:伴神经内分泌分化的非小细胞肺癌具有较高凋亡活性,是其对放、化疗敏感的生物学基础,Apaf-1和Caspase-3高表达发挥了重要作用。     

芦荟多糖增强顺铂对肺腺癌裸鼠移植瘤生长的抑制作用

目的 观察芦荟多糖（Aloe polysaccharide,AP）和顺铂（DDP）合用对人肺腺癌A549细胞裸小鼠移植瘤生长的抑制作用,并初步探讨其作用机制。方法 采用A549细胞株建立人肺腺癌裸鼠模型,将35只,♀,成瘤裸小鼠随机分为7组：对照组（生理盐水0.2 mL）;DDP低剂量组（1.0 mg·kg^-1）;DDP高剂量组（5 mg·kg^-1）;AP低剂量组（10 mg·kg^-1）;AP高剂量组（30 mg·kg^-1）;DDP低剂量组＋AP低剂量组;DDP低剂量组＋AP高剂量组,隔天腹腔注射给药,共8次。于最后1次给药后48 h处死各组小鼠,收集瘤标本行光镜观察,免疫组化检测p53和bcl-2蛋白表达情况。结果 各实验组肿瘤的生长明显受到抑制,瘤质量明显低于对照组（P〈0.01）。低、高剂量AP联合用药组较低剂量DDP组抑瘤作用明显增强（P〈0.05）,其瘤重抑制率分别为49.34%和82.61%。高剂量AP组与对照组比较,p53和bcl-2的表达均下调,差异具有统计学意义（P〈0.05）,联合用药组该调节作用进一步增强。高剂量DDP组出现不良反应,其余各组无明显不良反应。结论 AP能够增强DDP对人肺腺癌A549细胞裸鼠移植瘤生长的抑制作用,其作用机制可能与AP抑制p53和bcl-2的表达有关。     

α1,3 FUCT Ⅶ mRNA及Sle~x抗原在非小细胞肺癌组织中的表达及其与转移的关系

目的探讨α1,3FUCT Ⅶ基因mRNA及Slex在非小细胞肺癌组织,癌旁正常肺组织中的表达,及其与临床病理因素的关系。方法应用RT-PCR法及免疫组织化学催化放大法(CSA)检测α1,3FUCT Ⅶ基因mRNA734.2及Slex在66例非小细胞肺癌组织,20例癌旁正常肺组织中的表达。结果α1,3FUCT Ⅶ基因mRNA在腺癌组织(0.79±0.19)强于鳞癌组织中(0.51±0.12),差异有统计学意义(P*<0.05)。Slex的表达在腺癌阳性率为86%(31/36),鳞癌为63.3%(19/30),差异有统计学意义(P*<0.05)。α1,3FUCTⅦ基因mRNA及Slex的表达与TNM分期、分化程度、淋巴结转移、组织学类型及性别有关,与年龄无关(P>0.05)。结论α1,3FUCT Ⅶ基因mRNA及Slex过表达可能与非小细胞肺癌发生及转移相关,其检测可作为判断患者肺癌转移的一项重要参考指标。     

Effect of atorvastatin on tumor growth and metastasis in a breast cancer cell xenograft model and its mechanism

This paper aims to evaluate the effects and the possible mechanisms of atorvastatin on tumor growth and metastasis in a xenograft tumor model. Twenty-four female athymic BALB/C mice with MDA-MB-435 xenograft tumors were randomly assigned to three groups: a control group, a low-dose atorvastatin treatment group, and a high-dose atorvastatin treatment group. The mice in the treatment groups began to be administered with atorvastatin (10 or 20 mg/kg per day) when the xenograft tumors reached 1 cm in diameter. At the end of the experiment, the tumor volume and weight and the lung metastasis colonies of each mouse were measured. Western blotting was applied to detect phosphorylation of protein kinase B (PKB, Akt), extracellular signal regulated kinase (ERK), c-Jun N-terminal Kinase (JNK), and the expression of cytochrome P450 (CYP) subtype CYP2J2. Atorvastatin suppressed xenograft tumor growth and metastasis both in the low-dose and the high-dose treatment groups (P < 0.05). Atorvastatin also decreased the phosphorylated Akt (p-Akt) and p-ERK but increased p-JNK expression. However, atorvastatin did not alter the expression of CYP2J2 in tumor tissue. This suggests that atorvastatin has the efficacy of suppressing tumor growth and metastasis in vivo. These effects were not dependent on down-regulation of CYP2J2 expression.     

Modulation of murine tumor growth and colonization by bromelaine, an extract of the pineapple plant (Ananas comosum L.)

The antitumor and antimetastatic activities of the plant cysteine endoproteinase bromelaine were evaluated in a murine model. Syngeneic sarcoma L-1 cells were incubated with bromelaine (after preceeding time and dosage kinetics) and subcutaneously; (s.c.) or intravenously; (i.v.) inoculated into BALB/c-mice (n = 5 per experimental group) to induce local tumor growth or lung colonization. Compared to non-protease incubated L-1 cells, local tumor growth and experimental lung metastasis decreased significantly (p < 0.05). After bromelaine incubation of the tumor cells. Sarcoma L-1 cells induced local tumor growth after s.c. inoculation and lung colonization after i.v. injection. Intraperitoneal (i.p.) or s.c. administration of bromelaine (optimal dosage and time schedule tested in preceeding kinetic studies) significantly (p < 0.05) reduced local tumor weight, however, lung colonization was non-significantly reduced. Bromelaine incubation of sarcoma L-1 cells significantly reduced their tumorigenic/metastatic capacities. Bromelaine treatment after tumor cell inoculation significantly reduced local tumor growth, experimental lung metastasis, however, to a lesser, non-significant degree.     

Caveolin-1和Survivin在结直肠腺癌组织中的表达及其意义

目的探讨Caveolin-1和Survivin在结直肠腺癌组织中的表达及其意义,为结直肠癌判断预后及多途径治疗提供有效的试验依据。方法采用免疫组织化学方法,检测116例结直肠腺癌和正常结肠组织Caveolin-1与Survivin的表达,分析与临床病理参数的关系。结果 Caveolin-1在结直肠腺癌中表达降低,与肿瘤分化程度、浸润深度、淋巴结转移、Dukes分期相关。Survivin在结直肠腺癌组织表达增多,其阳性表达与肿瘤的不同的分化程度、浸润深度、Dukes分期及有无淋巴结转移相关。结论 Caveolin-1和Survivin的表达可能与结直肠腺癌的发生、发展密切相关,二者可作为评价结直肠腺癌预后的指标,对结直肠腺癌的治疗有重要意义。     

Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinicopathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell cancer, 16 cases of lung adenocarcinoma) and tumor-surrounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumorsurrounding normal lung tissues, respectively. The expression level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues (P = 0.000). The Syk expression was positively correlated with the p53 expression in NSCLC specimens (P = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.     

Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53-p21-Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity.     

茯苓多糖对Lewis肺癌小鼠自发肺转移的抑制作用及其机制研究

目的 研究茯苓多糖对Lewis肺癌小鼠自发肺转移的影响,并探讨其作用机制。方法 C57BL/6小鼠右腋皮下接种Lewis肺癌细胞,分为茯苓多糖高（0.50 mg/只）、低（0.33 mg/只）剂量组,顺铂组（顺铂0.04 mg/只）,模型组（生理盐水）,接种瘤细胞后第2天开始尾iv给药,隔天一次。观察小鼠一般状态,造模后第7天开始,隔天测量肿瘤体积。造模后21 d取肺,计数肺表面转移灶个数,HE染色检测肺微小转移灶个数,检测外周血白细胞数量及脾质量、脾指数。结果 茯苓多糖高、低剂量对实体瘤无明显抑制,茯苓多糖高剂量可减少肺表面转移灶个数,增加白细胞CD11bmRNA表达,不影响外周血白细胞数、脾质量及脾指数,一般状况较好;茯苓多糖低剂量对肺表面转移灶个数、外周血白细胞数、脾质量及脾指数无明显影响,可增加白细胞CD11b、CD18mRNA表达,一般状况较好。结论 茯苓多糖对Lewis肺癌小鼠实体瘤无明显抑制作用,但能够抑制其自发肺转移,对外周血白细胞数量、脾质量及脾指数无明显影响,可增加外周血白细胞CD11b、CD18mRNA表达,活化外周血白细胞可能是茯苓多糖抑制肿瘤转移的机制之一。     

Inhibition of transforming growth factor beta signaling reduces pancreatic adenocarcinoma growth and invasiveness

Transforming growth factor beta (TGFbeta) is a pleiotropic factor that regulates cell proliferation, angiogenesis, metastasis, and immune suppression. Dysregulation of the TGFbeta pathway in tumor cells often leads to resistance to the antiproliferative effects of TGFbeta while supporting other cellular processes that promote tumor invasiveness and growth. In the present study, SD-208, a 2,4-disubstituted pteridine, ATP-competitive inhibitor of the TGFbeta receptor I kinase (TGFbetaRI), was used to inhibit cellular activities and tumor progression of PANC-1, a human pancreatic tumor line. SD-208 blocked TGFbeta-dependent Smad2 phosphorylation and expression of TGFbeta-inducible proteins in cell culture. cDNA microarray analysis and functional gene clustering identified groups of TGFbeta-regulated genes involved in metastasis, angiogenesis, cell proliferation, survival, and apoptosis. These gene responses were inhibited by SD-208. Using a Boyden chamber motility assay, we demonstrated that SD-208 inhibited TGFbeta-stimulated invasion in vitro. An orthotopic xenograft mouse model revealed that SD-208 reduced primary tumor growth and decreased the incidence of metastasis in vivo. Our findings suggest mechanisms through which TGFbeta signaling may promote tumor progression in pancreatic adenocarcinoma. Moreover, they suggest that inhibition of TGFbetaRI with a small-molecule inhibitor may be effective as a therapeutic approach to treat human pancreatic cancer.     

尼克酰胺-N-甲基转移酶在肺腺癌间质中的表达及其生物学功能 #br#

目的 探讨尼克酰胺-N-甲基转移酶（NNMT）在肺腺癌间质中的表达水平及过表达NNMT对肺腺癌细胞 生物学功能的影响。方法 （1）收集150例肺腺癌患者手术切除的组织标本。免疫组织化学染色检测癌组织和间质 细胞中 NNMT 的表达水平,并分析其表达与患者临床病理特征及预后间的关系。（2）分别转染过表达 NNMT 质粒 （NNMT组）和对照质粒（control组）构建稳定表达NNMT的肺成纤维细胞系HFL-1,采用荧光定量PCR（qPCR）、细胞 免疫荧光、蛋白质印迹法（Western blot）检测NNMT表达水平。（3）收集过表达NNMT及control组HFL-1细胞的培养 上清,分别和肺腺癌A549、PC9细胞进行共培养,通过细胞增殖实验、平板克隆形成实验、Transwell侵袭实验以及划 痕愈合实验比较2种培养液对A549、PC9细胞增殖、克隆形成、迁移及侵袭能力的影响。结果 （1）免疫组化染色显 示,150例患者组织标本中65例癌细胞中NNMT呈高表达,83例间质细胞中NNMT呈高表达。有淋巴结转移和病理 分期Ⅲ~Ⅳ期患者肿瘤间质细胞中NNMT高表达比例较高,且肿瘤间质中高表达NNMT患者的总生存率明显低于低 表达者。（2）成功构建了稳定过表达 NNMT 的 HFL-1 细胞,Western blot、qPCR、细胞免疫荧光染色均提示 NNMT 组 NNMT表达高于control组。（3）细胞共培养结果显示,与control组相比,表达NNMT的肺成纤维细胞系的培养液可以 显著促进A549和PC9细胞的增殖、克隆形成、迁移以及侵袭。结论 肿瘤间质表达的NNMT与肺腺癌的恶性进展密 切相关,可能是肿瘤靶向生物治疗的潜在靶点。     

ABCG2作为肺癌干细胞标志的意义探讨

目的:探讨干细胞标志物ABCG2作为肺癌干细胞标志的意义。方法:常规石蜡包埋、切片及HE染色,应用免疫组化SP法检测ABCG2在肺癌组织及肺癌细胞系GLC-82和A549中的定位和表达。显微镜观察ABCG2蛋白表达的部位及分布,用Lei-caQ500MC图像分析系统对其表达强度的阳性单位(positive unit PU)进行定量测试分析。结果:ABCG2蛋白表达在肺癌细胞的胞质和胞膜;肺癌组织中肺鳞癌和肺腺癌呈阳性表达,弥漫分布;肺大细胞癌和肺小细胞癌不表达。ABCG2蛋白表达阳性率和表达强度在肺腺癌中表达最高,其次为肺鳞癌,肺小细胞癌及肺大细胞癌表达最低(P<0.05),且两者之间表达差异无显著性(P>0.05)。ABCG2蛋白在肺癌淋巴结转移灶中的表达特点与原发灶一致,但转移灶中腺癌和鳞癌表达阳性率的差异无显著性(χ2=0.36,P>0.05)。ABCG2蛋白在肺癌细胞系GLC-82和A549中呈弥漫阳性表达。结论:ABCG2单独不适合作为肺癌干细胞的标志物,但可作为肺癌分型的标记物。     

和厚朴酚及厚朴酚抗肺癌药理作用及机制的研究进展

和厚朴酚及厚朴酚是疏水性烯丙基联苯酚类结构的同分异构体,均有抗肺癌药理作用。和厚朴酚能抑制肺癌A549细胞、H1299细胞和Lewis细胞移植瘤在小鼠体内的生长和转移,而厚朴酚能预防乌拉坦诱导小鼠发生肺癌和抑制A549细胞移植瘤在小鼠体内生长。和厚朴酚及厚朴酚在体外能浓度相关地抑制人小细胞肺癌N446细胞、H446细胞,非小细胞肺癌中的肺腺癌A549、H1299、H441、H1975、Calu3、A2、PC、SPC-A-1、95D细胞,大细胞肺癌H460细胞,人肺鳞癌H226、H520、CH27细胞以及小鼠肺癌Lewis细胞增殖,并诱导其凋亡和坏死。和厚朴酚及厚朴酚抑制肺癌的主要机制是：（1）抑制I型去乙酰化酶的表达和酶活性,上调死亡受体-5（DR5）的表达,激活肿瘤坏死因子相关的凋亡诱导配体（TRAIL）信号通路;（2）激活与半胱天冬酶无关的凋亡通路;（3）阻滞癌细胞中的微管聚合,破坏微管结构;（4）阻滞蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路,诱导癌细胞自噬;（5）阻滞磷脂酰肌醇-3激酶（PI3K）/AKT信号通路而抑制癌细胞转移。     

Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma

Fibroblast growth factor (FGF)-9 belongs to the FGF family which modulate cell proliferation, differentiation, and motility. Benzo(a)pyrene is a polycyclic aromatic hydrocarbon (PAH) and ubiquitous environmental carcinogen present in automobile exhaust, cigarette smoke, and foods. The major purposes of this study were to explore the roles of FGF-9 in the benzo(a)pyrene-induced lung cancer invasion in vitro and the metastatic development of lung adenocarcinoma in human. The data of RT-PCR analysis indicated that treatments of human lung adenocarcinoma CL5 cells with benzo(a)pyrene and a PAH mixture motorcycle exhaust particulate (MEP) extracts increased FGF-9 mRNA expression. The increased expression was blocked by cotreatments with a p38 mitogen-activated protein kinase inhibitor SB202190 and an extracellular signal-regulated kinase inhibitor PD98059. The results of immunoblot analysis and Matrigel assay showed that benzo(a)pyrene and MEP extracts produced a concomitant induction of FGF-9 protein and invasive ability of CL5 cells. The benzo(a)pyrene- and MEP-induced invasion was suppressed by FGF-9 neutralizing antibodies. The results of immunohistochemistry analysis of human lung adenocarcinoma specimens showed that FGF-9 protein was detected in the adenocarcinoma cells but not in normal epithelium. FGF-9 staining intensity was positively correlated with status of disease and degree of lymph node metastasis in these lung adenocarcinomas. These present findings suggest that FGF-9 has potential roles in benzo(a)pyrene-induced CL5 cell invasion and human lung adenocarcinoma metastasis.     

Inhibitory effect of topiramate on Lewis lung carcinoma metastasis and its relation with AQP1 water channel

AIM: To study the effect of topiramate on tumor metastasis and its relation with aquaporin 1 (AQP1) water channel. METHODS: Lewis lung carcinoma metastatic model was used to determine the effect of topiramate on tumor growth and metastasis. Colorimetric estimation was used to investigate the action of topiramate on carbonic anhydrase (CA) activity. Western blotting and immunohistochemical analysis were used to study the influence of topiramate on AQP1 water channel expression in lungs or tumor tissues of mice bearing Lewis lung carcinoma.     

Human MCAF Gene Transfer Enhances the Metastatic Capacity of a Mouse Cachectic Adenocarcinoma Cell Line in Vivo

Purpose. To evaluate the effect of monocyte chemotactic and activating factor (MCAF/MCP-1/JE) on tumor progression and metastasis. Methods. Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCAF expression vector. Spontaneous lung metastases were determined in mouse. Results. The production of MCAF reached 0.4 ng/ml in vitro when transfectant cells were cultured at a cell density of 5 × 10⁴ cells/ml for 3 days. Transfection of MCAF expression vector did not affect the growth rate in vitro. Also, after MCAF-transfection, the size of tumors after intra-footpad inoculation was similar to that of the parental cells. When the primary tumors were resected on the 10th day after inoculation, the incidence of spontaneous lung metastasis was less than 20% in both cells. The number of endothelial cells in the primary tumor rapidly increased from the 10th to the 14th day after inoculation, as revealed by immunohistochemical staining. In accordance with enhanced angiogenesis, the incidence rates of spontaneous metastasis increased when the primary tumors were resected on the 14th day after inoculation. Moreover, the spontaneous lung metastases were augmented in the animals injected with MCAF-transfectants compared to those injected with parental cells with a concomitant increase of angiogenesis. Conclusions. These results suggest that MCAF may augment the metastatic potential by modulating tumor associated angiogenesis.     

灵芪胶囊对小鼠Lewis肺癌移植瘤的抑制作用 及对相关血管生成因子表达的影响

［摘要］目的通过建立小鼠Lewis肺癌移植瘤模型，探讨灵芪胶囊对移植瘤生长、转移及其相关血管生成因子的作用。方法以Lewis肺癌荷瘤小鼠为研究对象，检测灵芪胶囊对转移瘤和肺转移灶的抑制率。应用S P免疫组织化学方法，检测灵芪胶囊对荷瘤小鼠血管生成因子碱性成纤维细胞生长因子（bFGF）、环氧化酶（COX） 2表达的影响。用分光光度计测量灵芪胶囊对荷瘤小鼠血清中诱生型一氧化氮合酶（iNOS）含量的影响。结果灵芪胶囊对Lewis肺癌荷瘤小鼠表现出明显抑瘤作用，其高、中、低剂量抑瘤率分别为35.64%，29.23%，21.03%，并与复方环磷酰胺合用有明显的增效减毒作用。同时，灵芪胶囊可有效抑制肺癌转移，能够下调血管生长因子bFGF和COX 2的表达，并降低血清中的iNOS含量而抑制肺癌血管生成，从而发挥抗转移作用。结论灵芪胶囊具有抑制小鼠Lewis肺癌移植瘤生长和转移的作用，其作用机制可能与下调COX 2和血管生成因子的表达及降低血清中的iNOS含量有关。