海参皂苷Echinoside A和ds-Echinoside A抑制小鼠Lewis肺癌生长和转移作用

目的探讨海参皂苷Echinoside A(EA)和ds-Echinoside A(DSEA)对小鼠肿瘤生长和自发肺转移的抑制作用及机制。方法建立C57BL/6J小鼠Lewis肺癌自发性肺转移模型,连续腹腔注射给药21 d,剥离原位肿瘤和双侧肺,分别称瘤重和计数肺表面转移灶结节数;采用RT-PCR法检测肿瘤组织中半胱氨酸蛋白水解酶3(Cysteine-requiring Aspartate Protease,Caspase 3)、基质金属蛋白酶-2/9(matrix metalloproteinase-2/9,MMP-2/9)、金属蛋白酶组织抑制剂-1/2(tissue inhibitor of metalloproteinase-1/2,TIMP-1/2)、乙酰肝素酶(heparanase,HPA)和血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA的表达。结果 EA和DSEA均能抑制Lewis肺癌小鼠移植瘤的生长,并显著抑制减少肺表面转移灶结节数。EA和DSEA可以显著提高荷瘤小鼠肿瘤组织中Caspase 3和TIMP-1/2mRNA的表达,降低MMP-2/9、HPA和VEGF mR-NA的表达(P<0.05,P<0.01)。结论 EA和DSEA能显著抑制小鼠Lewis肺癌生长和自发性肺转移,其机制可能与诱导肿瘤细胞凋亡,调节细胞外基质(extracellular matrix,ECM)降解相关基因的表达、抑制VEGF的释放,从而抑制肿瘤细胞的转移和血管新生有关。     

海参岩藻聚糖硫酸酯抗肿瘤转移作用研究

目的建立小鼠黑色素瘤B16细胞实验性肺转移模型,探讨海参岩藻聚糖硫酸酯(sea cucumber fu-coidan,SC-FUC)的体内抑制肿瘤肺转移作用。方法连续腹腔注射SC-FUC 26d后,检测小鼠肺转移灶数量、血清中唾液酸的含量、γ-谷氨酰转肽酶活力和肺组织中羟脯氨酸、氨基己糖、糖醛酸的含量。结果SC-FUC剂量组小鼠的肺转移灶数量显著减少(P<0.01),平均转移抑制率为65.25%,血清唾液酸含量和γ-谷氨酰转肽酶活力显著降低(P<0.01),肺组织中羟脯氨酸、氨基己糖、糖醛酸的含量显著下降(P<0.01)。结论SC-FUC能显著抑制肿瘤细胞在小鼠体内的转移和生长。     

泰素抑制涎腺腺样囊性癌远处转移的机制研究

目的:观察泰素(Taxol)对涎腺腺样囊性癌细胞远处转移的作用及其对肺转移灶血管内皮生长因子(VEGF)、基质金属蛋白酶(MMP-9)表达的影响.方法:用涎腺腺样囊性癌肺高转移细胞株(ACC-M)裸鼠肺转移模型观察泰素体内抗转移效果,免疫组化法检测转移灶肿瘤细胞VEGF和MMP-9的表达.结果:对照组与Taxol治疗组相比,2组之间瘤结节数差异有统计学意义(P＜0.05);Taxol治疗组VEGF及MMP-9表达明显弱于对照组(P＜0.05).结论:泰素对涎腺腺样囊性癌肺转移有较好的抑制效果,这可能与其抑制血管生成及基质金属蛋白酶表达有关.     

开口箭皂苷抗黑色素瘤侵袭与转移作用研究

目的研究开口箭皂苷对B16-BL6黑色素瘤肺转移和体外肿瘤细胞穿透人工基底膜的影响。方法小鼠爪下制备黑色素瘤模型,注射不同剂量开口箭皂苷溶液,3周后称量患肢质量并计算肿瘤抑制率,5周后测定小鼠肺、脾、胸腺组织表面肿瘤节结数,Transwell小室实验测定药物对肿瘤细胞侵袭基底膜的影响。结果开口箭皂苷呈剂量依赖性地抑制小鼠黑色素瘤生长,高剂量(45 mg.kg-1)开口箭皂苷可明显减少小鼠肺转移结节数、总转移结节数和转移率(P<0.05);Transwell小室实验中,开口箭皂苷可显著抑制侵袭细胞数(P<0.05),抑制率21.46%。结论开口箭皂苷可能通过抑制黑色素瘤生长、转移及降低基底膜侵袭而发挥抗肿瘤作用。     

乳腺癌组织中ING4、HIF-1α和HIF-2α表达及与肿瘤微血管新生的关系

目的 探讨乳腺癌组织中生长抑制因子4(ING4)、缺氧诱导因子-1α(HIF-1α)和缺氧诱导因子-2α(HIF-2α)表达及与肿瘤微血管新生的关系.方法 选取择期行手术治疗的乳腺癌病人107例,利用实时荧光定量PCR技术检测乳腺癌和癌旁组织中HIF-1α、HIF-2α、ING4和血管内皮生长因子(VEGF)基因表达,免疫组化染色检测乳腺癌和癌旁组织中微血管密度(MVD).结果 乳腺癌组织中HIF-1α mRNA、HIF-2α mRNA相对表达量均高于癌旁组织,而ING4 mRNA 相对表达量低于癌旁组织,差异有统计学意义(P<0.05);HIF-1α mRNA相对表达量与淋巴结转移有关(P<0.05),HIF-2α mRNA相对表达量与肿瘤大小、淋巴结转移有关(P<0.05),ING4 mRNA相对表达量与临床分期、淋巴结转移有关(P<0.05);乳腺癌组织中VEGF mRNA相对表达量和MVD计数均高于癌旁组织,均差异有统计学意义(P<0.05);Pearson相关分析显示,乳腺癌组织中HIF-1α mRNA、HIF-2α mRNA相对表达量均与VEGF mRNA相对表达量和MVD计数呈正相关(r=0.382、0.417和0.408、0.491,P<0.05),ING4 mRNA相对表达量均与VEGF mRNA相对表达量和MVD计数呈负相关(r=-0.395、-0.502,P<0.05).结论 乳腺癌组织中HIF-1α、HIF-2α基因表达升高,而ING4基因则被抑制,可能共同参与了乳腺癌组织中血管新生.     

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。     

康莱特注射液抗恶性肿瘤肝转移疗效及机制的实验研究

目的通过接种W256癌肉瘤建立Wistar大鼠肝癌转移模型,观察康莱特注射液与肝动脉结扎法对大鼠荷瘤脾重与肝癌转移灶的抑制效果,并测定其对瘤组织内基质金属蛋白酶(MMP-1)及肝细胞生长因子(HGF)表达的影响,探讨中西医结合防治肝癌转移的新途径。方法在Wistar大鼠脾下极注射W256癌肉瘤细胞悬液,建立肝癌转移模型。随机分4组:对照组、动脉结扎组、康莱特组、康莱特+动脉结扎组。计算各组瘤重抑制率与肝癌转移抑制率,采用原位杂交技术检测肿瘤细胞内MMP-1和HGF mRNA表达水平。结果康莱特和康莱特加动脉结扎组均显著抑制脾脏肿瘤生长并抑制肝脏瘤组织MMP-1 mRNA表达,康莱特组能明显抑制肝癌转移灶产生,各治疗组大鼠瘤细胞HGF mRNA表达水平均低于对照组。结论康莱特注射液可显著抑制原发灶生长与肝癌转移灶的形成,抑制瘤细胞MMP-1表达是其抗肝转移的重要机制;康莱特注射液结合动脉结扎可使瘤细胞MMP-1表达减少,提示可优化两者结合途径。     

EMMPRIN-MMPs-VEGF系统在乳腺癌移植瘤模型中的表达

【摘要】 目的 研究细胞外基质金属蛋白酶诱导因子（EMMPRIN）-基质金属蛋白酶（MMPs）-血管内皮生长因子（VEGF）系统在小鼠乳腺癌肺转移模型中的表达水平, 探讨该系统在乳腺癌生长和转移过程中的作用。 方法采用免疫组化 SP 法检测 EMMPRIN、 MMP-2、 MMP-9 和 VEGF 在小鼠乳腺癌肺转移模型组织中的表达。 结果EMMPRIN、MMP-2、MMP-9 和 VEGF在乳腺癌肺转移模型中呈现明显表达; 且转移组各项指标阳性表达率均高于非转移组（ P＜ 0.05）。 结论 EMMPRIN-MMPs-VEGF 系统各组分在小鼠乳腺癌肺转移模型中通过相互协同, 共同促进肿瘤细胞的生长、浸润和转移。     

新加沙参麦冬煎剂抑制肿瘤转移及其作用机制的实验研究

目的 探讨新加沙参麦冬煎剂防治肿瘤转移的机制。方法结合动物模型、免疫组化、细胞分子生物学技术，观察新加沙参麦冬煎剂对荷瘤小鼠抑瘤率、转移抑制率、生命延长率的影响，检测实验小鼠皮下移植瘤血管内等细胞生长因子（VEGF）、血管内皮细胞第Ⅷ因子（CD34）、黏附因子（CD44V6）、基质金属蛋白酶2（MMP2）、基质金属蛋白酶抑制酶（TIMP2）的表达情况。结果新加沙参麦冬煎剂治疗组的瘤重抑制率、肺转移抑制率、生命延长率分别为37.3%，58.3% 和20.8%；皮下移植瘤CD44V6 、VEGF表达、微血管密度（MVD）明显低于空白组（P＜0.01），TIMP2表达记分明显高出其他组（P＜0.01）。小鼠肺转移灶数与VEGF 、CD44V6、MVD呈线性相关，相关系数分别为0.490，0.398，0.455。结论①新加沙参麦冬煎剂对小鼠LA795高转移肺腺癌模型有较好抑制转移、抑制肿瘤生长和延长荷瘤小鼠生存时间的作用。②新加沙参麦冬煎剂可通过调控肿瘤转移过程中黏附、基质降解、血管生成相关分子的表达，多途径、多靶点防治肿瘤的转移。     

靶向HIF—1α小干扰RNA对裸鼠MiaPaCa2细胞移植瘤生长的影响

目的:初步探讨重组腺相关病毒(rAAV)介导的靶向缺氧诱导因子-1α(HIF-1α)小干扰RNA对裸鼠Mia-PaCa2人胰腺癌细胞移植瘤生长的影响.方法:首先构建rAAV介导的以HIF-1α为靶基因的RNA干扰表达载体,即rAAV-siHIF.将rAAV-hrGFP、rAAV-siHIF分别转染对数生长的MiaPaCa2细胞,在乏氧条件下进行培养,应用Real-Time PCR、Western Blot和ELISA法观察其对MiaPaCa2细胞HIF-1α mRNA、蛋白和VEGF表达的影响.将MiaPaCa2细胞接种于裸鼠皮下,形成荷瘤小鼠后随机分别肌注ddH2O(空白对照组)、rAAV-hrGFP(空载病毒组)和rAAV-siHIF(干扰病毒组),30 d后处死荷瘤裸鼠,取出移植瘤并测量肿瘤的大小及肿瘤的质量,应用免疫组化染色观察各组肿瘤标本HIF-1α、VEGF、CD34的表达并计数微血管密度(MVD).结果:体外实验发现,干扰病毒组MiaPaCa2细胞HIF-1α mRNA和蛋白的表达以及VEGF的分泌低于空白对照组(均P<0.01).体内实验发现,干扰病毒组裸鼠移植瘤的生长和HIF-1α、VEGF及CD34的表达也低于空白对照组(P<0.01或P<0.05).而空载病毒组与空白对照组相比,体内外实验结果差别均无统计学意义(均P>0.05).结论:rAAV介导的靶向HIF-1α小干扰RNA有抑制裸鼠MiaPaCa2细胞移植瘤生长的作用,其机制可能是通过抑制移植瘤的血管生成而实现的.     

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。     

Antiangiogenic effect of berberineα-hydroxy-δ-decanoylethyl sulfonate on Lewis lung carcinoma

OBJECTIVE To investigate the antiangiogenic and antitumor effects of berberineα-hydroxy-δ-decanoylethyl sulfonate(HB)in vitro and in vivo.METHODS MTT assay was employed to determine the proliferation of tumor cells.Western blot analysis was used to detect the expression of VEGF and MMP-9.Transwell co-culture was used to determine the cell migration at the conditioned medium of Lewis lung carcinoma cells exposed to HB for 24 h.The C57BL/6 mice bearing Lewis lung carcinomas were treated with vehicle,different doses of HB(60,90 and 120mg·kg-1,ig)for 20 d,or cyclophosphamide(50mg·kg-1,ig)at d 1,d 8 and d 15.Afterwards,the xenografted tumors were exercised and weighed,and the lung metastasis was determined by HE stainingof the lung tissues.Tumor angiogenesis was determined by CD34 staining and microvessel density(MVD)by immunohistochemistry.RESULTSHB inhibited the growth of Lewis lung carcinoma cells in a time-dependent manner with IC50 value of 8.87,2.26 and 0.98mg·L-1,respectively when the cells were treated with HB for 24,48 and 72h.Cell migration induced by the conditioned medium of Lewis lung carcinoma cells treated with 2.5,5 and 10mg·L-1 HB was reduced by 37%,54% and 63%respectively(P<0.01).HB suppressed the expression of angiogenesis factors in a concentration-dependent manner.HB was effective in inhibition of MMP-9 expression at 5,10 and 20mg·L-1(P<0.05),whereas HB 20mg·L-1 was minimal effective concentration in inhibition of VEGF expression(P<0.01).On C57BL/6 mice bearing Lewis lung carcinomas,HB significantly reduced the tumor burden and MVD in tumor mass as well as inhibited lung metastasis at doses of 90 and 120mg·kg-1.CONCLUSION HB produces reliable antiangiogenic effect,inhibits the growth and metastasis of Lewis lung carcinoma.These effects may be attributed to its ability of suppressing the expression of VEGF and MMP-9,and reducing MVD.     

Saikosaponins-b suppresses tumor growth and angiogenesis of hepatocellular carcinoma by regulating VEGF/ERK/HIF-1α signal pathway

OBJECTIVE Angiogenesis therapy has attracted interest as a potential treatment for hepatocellular carcinoma(HCC).In this study,we investigated the anti-proliferative activities and antiangiogenesis effects of saikosaponins(SS)-b on hepatocellular carcinoma(HCC)and its regulation on VEGF/ERK/HIF-1 αsignal pathway.METHODS H22 hepatoma-bearing mice model and HepG-2 cells were used to study the anti-tumor and anti-angiogenesis effects of SS-b in vivo and in vitro.Pathological change of tumor tissue was observed by HE staining,the microvascular changes were detected by immunohistochemical method.The effects of SS-b on angiogenesis were examined by using the chick embryo chorioallantoic membrane(CAM)model.The effects of SS-b on proliferation,migration and invasion were investigated by MTT assay,scratch wound healing assay and transwell assay inhuman umbilical vein endothelial cell(HUVEC)and HepG2 cells in vitro.Vascular endothelial growth factor(VEGF),matrix metalloproteinase-2/9(MMP-2/9),hypoxia-inducible factor-1α(HIF-1α)expression and the phosphorylation of extracellular regulated kinase(ERK)were analyzed using RT-PCR and Westernblot.RESULTS SS-b effectively inhibited the tumor growth of H22 mice in vivo.The inhibitory rate of tumor was 49.1%,50.7%,66.1%in SS-b 5,10 and 20 mg·kg-1group respectively.HE staining results showed that SS-b induced tumor necrosis and nuclear dissolution in H22 mice.Moreover,SS-b also reduced the number of microvessels of tumor tissue in H22 mice significantly and suppressed the angiogenesis of CAM induced by b-FGF.SS-b had an obvious inhibitory effect on cell proliferation,migration and invasion of HUVEC cells and HepG-2 cells.These effects were associated with downregulation of the expression of MMP2/9 and suppression of VEGF/ERK/HIF-1αsignaling in H22 mice and Hep-G2 cells.CONCLUSION Our findings showed that SS-b exerts anti-tumor effects by inhibiting tumor angiogenesis via regulating VEGF/ERK/HIF-1α signal pathway in vivo and in vitro.     

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...     

Antimetastatic potential of vernolide-A, a sesquiterpenoid from Vernonia cinerea L

The inhibitory effect of vernolide-A (C(21)H(28)O(7)) on lung metastasis induced by B16F-10 melanoma cells was studied using C57BL/6 mice. Vernolide-A was administered in three different modalities such as simultaneously with tumor, prophylactic to tumor and after tumor development. Maximum inhibition in the metastasis was observed when vernolide-A was administered simultaneously with tumor. There was 89.39% inhibition of lung tumor nodule formation and 88.51% increase in the life span of metastatic tumor-bearing animals. Highly elevated levels of lung hydroxyproline, lung uronic acid, lung hexosamine, serum sialic acid, serum γ-glutamyl transpeptidase (GGT) and serum vascular endothelial growth factor (VEGF) in the metastatic control animals were found to be significantly lowered in the vernolide-A-treated animals. Histopathological analysis of lung tissues also correlated with these results. Vernolide-A administration downregulated the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, extracellular-signal-regulated kinase-1 (ERK-1), ERK-2 and VEGF in the lung tissue of B16F-10 melanoma challenged animals. In the in vitro system, vernolide-A showed a significant inhibition of invasion of B16F-10 melanoma cells across the collagen matrix. Vernolide-A treatment also inhibited the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. Vernolide-A could inhibit MMP-2 and MMP-9 protein expression in gelatin zymographic analysis of B16F-10 cells. (3)H-thymidine proliferation assay showed that vernolide-A could inhibit the proliferation of B16F-10 melanoma cells in vitro. These results indicate that vernolide-A could inhibit the metastatic progression of B16F-10 melanoma cells in mice.     

异甘草素对人鼻咽癌CNE2细胞裸鼠移植瘤模型的放疗增敏作用

目的：观察异甘草素对鼻咽癌裸鼠移植瘤放疗的增敏效应,并探讨其与乏氧诱导因子－1α（ HIF－1α）、血管内皮生长因子（ VEGF）表达水平之间的关系。方法取低分化鼻咽癌CNE2细胞接种于雌性裸鼠皮下（共接种20只）,待肿瘤结节4～6 mm时,将裸鼠随机分为4组,分别为对照组、异甘草素组（50 mg? kg－1?周－1）、放疗组、异甘草素（50 mg? kg－1?周－1）联合放疗组。依照各组不同治疗措施处理,定期测量瘤体体积,20 d后处死裸鼠,剥离瘤体称重。分别计算4组抑瘤率。采用荧光定量PCR检测瘤体组织中HIF－1α及VEGF mRNA的表达水平。结果异甘草素联合放疗组移植瘤的体积和重量显著下降,与对照组、单纯异甘草素及单纯放疗组比较差异均有统计学意义（ P ＜0．05）;异甘草素联合放疗组HIF－1α、VEGF mRNA表达水平明显下降,与对照组及放疗组相比,差异有统计学意义（ P ＜0．05）。结论异甘草素能增强鼻咽癌裸鼠移植瘤对放疗的敏感性,其作用机制可能与抑制HIF－1α、VEGF表达水平,从而抑制肿瘤血管生成作用有关。     

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.     

Ad-ING4抑制人A549肺癌细胞及其裸鼠移植瘤的生长

目的 研究腺病毒介导的ING4基因(Ad-ING4)对肺癌体内外的抑制作用及其潜在的分子机制.方法 体外采用50 MOI的Ad-ING4感染A549肺癌细胞,并用MTT法检测Ad-ING4对A549细胞的抑制作用,流式细胞仪检测肿瘤细胞的凋亡率.采用A549细胞株建立人肺癌裸鼠模型,瘤体局部注射干预用药,每隔5天测量一次肿瘤体积,并计算瘤重抑瘤率;瘤块免疫组化检测ING4、生存素(survivin)、CD34、HIF-1等基因的表达.结果 Ad-ING4感染A549细胞抑制率可达47.62%;72 h凋亡率为18.5%;荷瘤裸鼠经治疗后,Ad-ING4组和顺铂(DDP)组的肿瘤体积、瘤重均明显缩小,其抑瘤率分别达到42.43%和46.47%,DDP组出现不良反应;免疫组化检测Ad-ING4组和DDP组与对照组比较,生存素、CD34、HIF-1的表达下调(P<0.01).结论 Ad-ING4对人A549肺癌细胞及其裸鼠移植瘤的生长具有明显的抑制作用.其抑瘤机制可能与下调生存素、CD34、HIF-1的基因表达进而诱导肿瘤细胞凋亡和抑制肿瘤血管形成等有关.