无POU域八聚体结合蛋白基因的克隆及其在Hepa 1-6细胞内的表达

目的 构建小鼠无POU域八聚体结合蛋白(non-POU-domain-containing,octamer binding protein,NonO)真核表达载体并在小鼠Hepa 1-6肝癌细胞内表达,观察NonO胞内表达、定位及脂多糖(LPS)对其定位的影响.方法 提取小鼠肝组织总RNA,RT-PCR扩增小鼠NonO基因的蛋白编码序列.采用基因重组技术将其亚克隆至pcDNA3-HA真核表达载体中,将该载体瞬时转染Hepa 1-6细胞,通过细胞免疫荧光方法观察NonO的胞内表达及LPS对其定位的影响.结果 酶切和DNA测序证明所构建质粒正确;细胞免疫荧光可见NonO在Hepa 1-6细胞内表达、分布于细胞核,LPS刺激后NonO分布无明显变化.结论 成功构建NonO真核表达载体,为研究NonO在基因表达调控中作用及其生物功能提供了重要载体.进一步证实NonO为定位于细胞核的核蛋白.     

秦皮乙素对小鼠皮下Hepa1-6肝癌移植瘤凋亡基因Bcl-2、Bax表达的影响

目的:研究秦皮乙素对小鼠皮下Hepa1-6肝癌移植瘤凋亡基因-2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达的影响。方法:40只C57BL/6J小鼠右腋皮下接种Hepa1-6肿瘤细胞,复制小鼠肝癌皮下移植瘤模型。实验分为5组,即模型(生理盐水)、环磷酰胺和秦皮乙素高、中、低剂量(700、400、200mg·kg-1)组。复制模型后第3天开始腹腔注射给药,15d后处死小鼠取出瘤组织,称瘤重,计算抑瘤率。RT-PCR检测凋亡基因Bcl-2mRNA、BaxmRNA的表达,Westernblot法检测Bcl-2蛋白、Bax蛋白表达。结果:秦皮乙素高、中、低剂量组抑瘤率分别为55.42%、40.37%、20.33%,与模型组比较有显著性差异(P<0.01);秦皮乙素高、中、低剂量组BaxmRNA和Bax蛋白的表达均显著高于模型组(P<0.01),Bcl-2mRNA和Bcl蛋白的表达均显著低于模型组(P<0.01)。结论:秦皮乙素对小鼠Hepa1-6肝癌瘤生长起到一定的抑制作用,其机制可能与通过上调Bax、下调Bcl-2基因的表达有关。     

共培养体系中小鼠囊胚对人卵巢癌细胞系HO-8910PM的影响

目的:观察两种具有侵袭特性的小鼠囊胚细胞与人卵巢癌细胞在相同的体外微环境下,动态的相互作用和整体生物学行为变化。方法:建立小鼠囊胚与人高转移卵巢癌细胞系HO-8910PM体外共培养模型,应用MTT法检测HO-8910PM细胞黏附率的改变;应用Transwell体外细胞侵袭实验观察HO-8910PM细胞体外侵袭及趋化性运动能力的变化;应用RT-PCR检测HO-8910PM细胞基质金属蛋白酶(MMP)-2、MMP-9、金属蛋白酶组织抑制剂(TIMP)-1、TIMP-2mRNA的表达。结果:癌细胞与小鼠囊胚共培养24h后,大部分囊胚开始边脱带边黏附,推开底层的癌细胞,在囊胚与肿瘤细胞间形成了明显的界限。共培养组的HO-8910PM细胞的黏附率低于对照组。Transwell小室体外侵袭实验及体外趋化性运动实验显示,共培养组穿过滤膜的细胞数明显少于对照组。共培养组MMP-2、MMP-9mRNA的表达及MMP/TIMP较对照组明显下降,TIMP-1、TIMP-2mRNA的表达略有增加。结论:当人HO-8910PM细胞与小鼠囊胚共培养时,肿瘤细胞失去了特有的侵袭性;小鼠囊胚能显著降低HO-8910PM细胞的黏附、体外侵袭能...     

乳腺癌中CD_(44)S和CD_(44)V_6基因蛋白表达的实验研究

<正>细胞黏附因子为一种细胞表面跨膜糖蛋白分子,分布于诸多细胞表面,包括淋巴细胞、单核细胞、RBC,成纤维细胞、上皮细胞、平滑肌细胞及肿瘤细胞等。CD44参与淋巴细胞的激活,以及细胞间透明质酸的特异性黏附,变异性CD44基因的多样性表达与肿瘤的生长、转移、复发等肿瘤生物学行为相关。我们应用免疫组化方法对乳腺癌中CD44S和CD44V6基因蛋白产物表达与组织学分型、脉管浸润、淋巴转移、预后、复发等相关性进行实验研究。1材料与方法1.1临床资料收集本院2000年1月至2010年12月间,161例原发性乳腺癌根治     

TIMP-1基因体外稳定转染对人卵巢癌A2780细胞周期与增殖的影响

目的:探讨正、反义基质金属蛋白酶组织抑制因子-1(TIMP-1)基因对人卵巢癌细胞周期及增殖的影响。方法:将重组质粒正、反义TIMP-1表达载体体外转染到卵巢癌A2780细胞中,用G418筛选稳定表达细胞株并扩增培养,采用MTT细胞计数法检测肿瘤细胞生长增殖率,流式细胞术检测肿瘤细胞周期的变化。结果:经15～20 dG418筛选得到稳定表达细胞株,重组质粒TIMP-1稳定转染正义(PTs)组A2780细胞的增殖可明显受到抑制,细胞周期明显改变,细胞从G1期到S期发生阻滞。而反义(PTas)组细胞与之相反。结论:提示体外转染TIMP-1基因可使A2780细胞周期阻滞于G1期,并可抑制肿瘤细胞增殖。可为临床基因治疗及相关基因药物研究提供实验依据。     

复方丹参对高转移性人肺癌细胞与血管内皮细胞黏附及黏附分子表达的影响

目的　探讨复方丹参抗肿瘤转移机理。方法　应用共聚焦显微镜和流式细胞仪荧光标记法,体外研究高转移性肺癌细胞(PG细胞)与血管内皮细胞的黏附性、黏附分子表达以及复方丹参抗肿瘤转移作用。结果　复方丹参可明显抑制PG细胞表面CD4 4 ,CD5 4的表达。复方丹参对PG细胞与激活和静息血管内皮细胞的黏附性也具有明显的抑制作用,并可抑制黏附分子CD4 4 ,CD4 5的表达,呈剂量依赖关系。结论　复方丹参具有抗肿瘤转移作用,抑制肿瘤细胞与内皮细胞黏附及黏附分子表达可能是复方丹参抗肿瘤转移的机制之一。     

重组pAd/CMV/V5-DEST-p16载体的构建及其对人肝癌细胞的抑制作用

目的构建pAd/CMV/V5-DEST-p16重组腺病毒载体,并观察野生型p16基因对人肝癌细胞SMMC7721株的抑制作用。方法合成人p16-INK4表达基因。构建pENTR 1A-p16质粒。通过LR反应,入口克隆pENTR 1A-p16质粒的外源性合成的修饰后的p16 cDNA,取代目的载体pAd/CMV/V5-DEST中的ccdB基因,形成表达克隆pAd/CMV/V5-DEST-p16。测序证实质粒含有目的基因。PacI酶切后的重组腺病毒载体,通过脂质体2000介导,转染293A细胞,产生缺陷性的重组腺病毒。W estern blot分析显示在由重组腺病毒介导的野生型p16基因在肝癌细胞SMMC7721中能够表达蛋白。被感染的细胞的生长受抑制。结果构建了重组p16腺病毒载体,产生缺陷性的重组腺病毒,野生型p16基因对人肝癌细胞SMMC7721株有抑制作用。结论用通路克隆系统构建重组p16腺病毒载体稳定、可靠、方便,腺病毒能够介导野生型p16基因在肝癌细胞中表达,并抑制细胞的生长。     

茶碱对嗜酸性粒细胞表面L选择素的脱落影响

目的:观察茶碱对嗜酸性粒细胞(Eos)表达L选择素(L-selectin)的影响.方法:采取15例正常人外周血,体外用不同浓度茶碱(10-3、10-4、10-5mol·L-1)和重组人白细胞介素(rhIL)-5(10-8 mol·L-1)预处理,以地塞米松(10-4 mol·L-1)为对照,用反转录-聚合酶链式反应(RT-PCR)和流式细胞仪法分别从mRNA和蛋白水平测定Eos L-selectin的表达及Eos的活化状态.结果:①茶碱和地塞米松均能抑制IL-5引起的Eos的活化和表面L-selectin的脱落;②茶碱对细胞内L-selectin mRNA水平无影响;③Eos的活化与L-selectin的脱落呈相关关系.结论:低于治疗浓度的茶碱即可抑制Eos表面L-selectin的脱落,并可能因此影响Eos的粘附功能.     

GHGKHKNK八肽抑制小鼠恶性黑色素瘤B16-F10转移及其机制的实验研究

目的：探讨GHGKHKNK八肽抑制小鼠恶性黑色素瘤B16-FIO细胞转移及其机制。结果：1．不同剂量的GHGKHKNK八肽对小鼠恶性黑色素瘤细胞B16-FIO的克隆形成均有抑制作用,与对照组相比较均有显著性差异（P〈0．05）2．不同剂量的GHGKHKNK八肽在体外作用24h后可以显著抑制小鼠恶性黑色素瘤B16-FIO细胞的侵袭,穿膜细胞数与对照组比较具有显著性差异（P〈0．05）。3．GHGKHKNK八肽在24h时5．5&#215;10^-4mol／L、5．5&#215;10^-5mol／L、5．5&#215;10^-6mol／L对小鼠恶性黑色素瘤细胞B16-F10黏附抑制率与对照组相比较均有显著性差异（P〈0．05）。4．经GHGKHKNK八肽作用后,小鼠恶性黑色素瘤细胞ICAM-1、LN—R表达降低表达降低,E-cadhesion表达增强。与对照组比较明显差异P〈0．05．5．GHGKHKNK八肽对B16一F10人工肺转移的抑制作用的实验结果显示：GHGKHKNK八肽各剂量组和环磷酰胺组肺转移灶的平均数目与生理盐水组照组相比较有明显差异（P〈0．05）：GHGKHKNK八肽500ug／kg／d、50ug／kg／d剂量组与环磷酰胺组对比有显著性差异（P〈0．05）。结论：i．GHGKHKNK八肽在体外能抑制小鼠恶性黑色素瘤细胞的体外克隆形成能力,能显著抑制小鼠恶性黑色素瘤B16-F10细胞的侵袭。提示HGKHKNK八肽可能通过抑制小鼠恶性黑色素瘤细胞的侵袭和增殖而抗肿瘤细胞的转移。2．GHGKHKNK八肽抑制小鼠小鼠恶性黑色素瘤细胞B16-FIO与人工基底膜的黏附,提示GFIGKHKNK八肽可能通过抑制细胞与基底膜的黏附来抑制肿瘤细胞的转移。3．GHGKHKNK八肽能够下调细胞间黏附因子1（ICAM-1）和层黏连蛋白受体（LN—R）在细胞内的表达,提示GHGKHKNK八肽可能通过抑制细胞间黏附因子的表达而抑制肿瘤细胞的转移。4．GHGKHKNK八肽能显著抑制小鼠恶性黑色素瘤细胞B16-F10在小鼠体内的肺转移。     

JWA基因在不同转移潜能人肝癌细胞中的表达及意义

目的 探讨JWA基因在不同转移潜能人肝癌细胞中的表达及意义.方法 分别应用荧光定量RT-PCR和Western blot法检测无转移潜能人肝癌细胞株Hep G2、低转移潜能人肝癌细胞株MHCC97L、高转移潜能人肝癌细胞株MHCC97H及较高转移潜能人肝癌细胞株HCCLM3的JWA mRNA和蛋白表达水平.结果 Hep G2细胞JWA mRNA和蛋白水平最高,HCCLM3细胞的JWA mRNA和蛋白水平最低,JWA基因表达水平随着肝癌细胞转移潜能增高而递减.结论 JWA mRNA和蛋白表达水平随着肝癌细胞转移潜能增高而递减,可能与肝癌的发生、发展及转移密切相关.     

Anti-metastatic potential of ginsenoside Rp1, a novel ginsenoside derivative

Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin with a chemopreventive action. In this study, we examined the anti-metastatic activities of G-Rp1 using relevant in vitro assays and in vivo metastasis models. Using a U937 cell-cell adhesion assay, we found that exogenously added G-Rp1 down-regulates beta1-integrin (CD29) activation at concentrations between 10 to 40 microM and suppresses the in vitro tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, this compound directly blocked cell viability of cancer cells such as A549 and HCT15 cells. In agreement with in vitro findings, G-Rp1 strongly inhibited the metastatic lung transfer of B16-F10 melanoma cells, which have a high surface level of beta1-integrins, without altering body weight. Therefore, these results suggest that G-Rp1 may act as an anti-cancer agent by strongly inhibiting cell viability and metastatic processes, presumably by inhibiting the adhesion of tumor cells and vessel formation.     

Inhibition of alpha(4) integrin mediated adhesion was involved in the reduction of B16-F10 melanoma cells lung colonization in C57BL/6 mice treated with gambogic acid

Gambogic acid, the major active ingredient of gamboge, has been shown to exhibit anti-cancer activity both in vivo and in vitro. However, its potential activity in tumor metastasis remains unclear. In the present study, we found that Gambogic acid strongly inhibited the adhesion of highly metastatic mouse melanoma B16-F10 cells in vitro. Gambogic acid also exhibited significant anti-metastasis activity on the development of in vivo artificial metastases (i.e. following tail vein i.v. injection of the B16-F10 melanoma tumor cells in C57BL/6 mice). Flow cytometric analysis and Western blot showed that Gambogic acid inhibited the cell surface expression of alpha(4) integrin, while exhibited negligible effects on the expression of alpha(5) and beta(1) integrin. Thus we concluded for the first time that Gambogic acid could inhibit the adhesion and migration of B16-F10 cells in vitro and in vivo, in which down-regulation of alpha(4) integrin expression was involved.     

Cancer metastasis: characterization and identification of the behavior of metastatic tumor cells and the cell adhesion molecules, including carbohydrates

This review focuses on the behavior of metastatic tumor cells and their specific adhesion molecules. Much of this review is based on the results from our researches over many years. Electron microscopic investigations of metastatic processes have demonstrated that desmosomes, tight junctions, or cell fusion-like structures are formed between tumor cells and other cells such as endothelial, mesothelial, hepatic, and nerve cells. These findings suggest that metastatic tumor cells acquire specific cell adhesion or recognition systems. To investigate these adhesion mechanisms, we established floating sublines from rat ascites hepatoma AH7974 in vitro and compared their adhesion molecules with those of their adherent counterparts. The anchorage independence of these tumor cells can be explained by reduced production of extracellular matrix proteins, decreased expression of cell surface integrin(s), or lack of heparan sulfate proteoglycans on the cell surfaces. Although the metastatic potential of these sublines for lung could not be explained by these properties, it may be explained by expression of 56 and 62 kDa laminin-like substances containing Griffonia Bandeirea simplicifolia isolectin B4-binding carbohydrate(s). We examined the relationship between carbohydrate expression and metastasis of human breast, pulmonary, colorectal, gastric, and other cancers by using a panel of lectins and monoclonal antibodies (MAbs). These studies revealed that several lectins and MAbs such as Vicia villosa agglutinin (VVA), Helix pomatia agglutinin, anti-sialyl Lewis(x-i) MAb, and others were useful not only for predicting metastasis and the prognosis of patients but also for understanding the routes of metastatic spread. VVA-binding carbohydrates, i.e. N-acetyl-D-galactosamine residues, especially those carried by atypical MUC1 protein, in aggressive cancer cells may serve as an important drug target.     

白细胞介素-24对宫颈癌Hela细胞裸鼠移植瘤的生长和淋巴转移的抑制作用及其与肿瘤转移相关基因-1表达变化的关系

目的探讨基因重组质粒pDC316-hIL-24对裸鼠人宫颈癌移植瘤生长和淋巴转移抑制的作用,以及其与肿瘤转移相关基因(MTA-1)表达变化的关系。方法建立裸鼠人宫颈癌Hela细胞移植瘤动物模型,成瘤后动物模型随机分为3组,每组6只:磷酸盐缓冲液组(PBS组),空质粒组(B组),白细胞介素(IL)-24重组质粒组(C组)。期间观察并记录各组裸鼠移植瘤的生长情况及肿瘤体积和裸鼠体质量的变化,绘制生长曲线。实验结束后处死各组裸鼠,剥取瘤体并称重,同时寻找淋巴转移灶,计算肿瘤生长抑制率、转移率。应用反转录-聚合酶链反应(RT-PCR)法和免疫组织化学法检测移植瘤IL-24的转录水平以及MTA-1基因表达的变化。结果 基因重组质粒pDC316-hIL-24转染成功,各组的抑瘤率分别为A组:0,B组:4.3%,C组:46.5%。IL-24组抑瘤率与其余两组相比差异有统计学意义(P<0.01),其生命活动和体质量无明显异常。IL-24组的淋巴转移率较对照组和空质粒组有显著下降趋势。免疫组织化学显示C组MTA-1基因表达下调差异有统计学意义(P<0.01)。结论 IL-24干预宫颈癌荷瘤裸鼠与其他各组相比较,其抑制移植瘤生长的作用明显,淋巴转移率降低,且无毒副作用,对MTA-1有抑制作用。     

A recombinant peptide, hirudin, potentiates the inhibitory effects of stealthy liposomal vinblastine on the growth and metastasis of melanoma

The metastasis of tumor cells is one of the major obstacles to successful clinical therapy. A treatment strategy by incorporating a specific inhibitor of thrombin, recombinant hirudin with stealthy liposomal vinblastine, was used in this study for inhibiting the metastasis of tumor cells and enhancing the efficacy of anti-tumor agents. In vitro cytotoxicity, cell adhesion to extracellular matrix (ECM) proteins, and cell invasion and migration assays were performed on human A375 melanoma cell line. In vivo measurement of coagulation parameters, inhibition of tumor growth, and inhibition of metastasis were assessed in female BALB/c mice. In vitro, vinblastine or stealthy liposomal vinblastine alone was effective to inhibit the growth of A375 cells. On the contrary, hirudin had no influence on either cytotoxicity when treating with hirudin alone or hirudin plus vinblastine. In addition, in vitro results showed that hirudin had no impact on the adhesion of tumor cells to extracellular matrix proteins, and metastasis and invasion of tumor cells. In mice, hirudin significantly inhibited the activity of thrombin. Furthermore, administered at the initial implantation of murine B16 melanoma cells, hirudin evidently delayed the growth of tumor, and depressed the occurrence of experimental lung metastasis. A subsequent administration of stealthy liposomal vinblastine resulted in further inhibiting growth and metastasis of tumor, indicating that hirudin plus stealthy liposomal vinblastine exhibited a significant anti-metastasis effect and slightly potent effect against tumor growth as compared with stealthy liposomal vinblastine alone. In conclusion, administration of recombinant hirudin followed by giving stealthy liposomal vinblastine may be beneficial for inhibiting the growth and metastasis of melanoma in vivo. The likely mechanism could be associated with inhibition of thrombin after administration of hirudin.     

GLB prevents tumor metastasis of Lewis lung carcinoma by inhibiting tumor adhesion actions

AIM: To investigate the inhibitory effect of a new compound of GLB on tumor metastasis in vivo and analyze its actions on tumor cell adhesion to clarify its mechanism. METHODS: The effect of GLB on tumor metastasis was analyzed by Lewis lung carcinoma model. The pathological morphology of lung alveolar was evaluated by hematoxylin-eosin staining. The effect of GLB on the proliferation of human prostate cancer cell (PC-3M, with a high metastatic characteristic) was studied using the MTT method, and its actions on PC-3M cell adhesion to human umbilical vein endothelial cells (HUVEC) and laminin were analyzed in vitro. RESULTS: GLB (100 mg/kg/d for 28 d, ig) reduced the number of lung colonies of Lewis lung carcinoma metastasis significantly (P<0.05). Simultaneously, GLB could mitigate the damage of lung alveolar caused by metastasic tumor deposits. In vitro, GLB inhibited dramatically the adhesion of PC-3M cells to HUVEC (P< 0.01) and laminin (P<0.05), without cytotoxic or anti-proliferative action on PC-3M cells. CONCLUSION: GLB has anti-tumor metastatic activity, which partly depends on its inhibition of tumor adhesion.     

整合素β_1和基质金属蛋白酶-2在胃癌中的表达及临床意义

目的通过应用免疫组化方法研究胃癌患者原发灶转移及邻近非肿瘤胃黏膜等不同组织的基质金属蛋白酶-2(MMP2)和整合素β1亚单位分布特征,旨在探讨整合素β1、MMP2的表达与胃癌侵袭性的关系,并指导临床治疗及判断胃癌患者的预后。方法采用免疫组织化学通用二步法检测整合素β1和MMP2在64例胃癌原发灶及其淋巴结转移灶中的表达情况。结果整合素β1在正常胃小凹表层上皮细胞膜表面呈均质性表达,并沿基底膜呈连续性线状分布;在胃癌组织的细胞浆和细胞膜呈棕黄色表达;淋巴结转移灶中呈非均质性棕黄色表达。在胃癌组织中的阳性表达率明显高于邻近的正常黏膜组织(P<0.05);在不同的组织学类型整合素β1阳性表达也有差异,在高中分化组为40%,在低分化组中为84.6%,可见,在低分化癌明显高于高中分化癌(P<0.01);整合素β1的阳性表达率与患者的年龄、性别、肿瘤的大小无明显相关性(P>0.05)。胃癌组织中MMP2阳性主要表达于胃癌组织的细胞浆和细胞膜内,呈棕黄色。MMP2表达阳性在胃癌组织明显强于邻近正常黏膜组织(P<0.05);浸透黏膜层组中的表达强于未浸透组(P<0.05);有淋巴结转移组的阳性表达高于无淋巴结转移组;不同的组织学类型中阳性表达也有差异,在低分化癌明显高于高中分化癌(P<0.01)。MMP2在胃癌中的表达与性别、年龄、肿瘤大小无关。结论整合素β1和MMP2的表达与胃癌的分化程度、侵润程度、淋巴结转移状况等临床病理因素密切相关,而与年龄、性别、肿瘤的大小等无关,其表达的检测对评估胃癌淋巴结转移程度有重要的意义,还可以作为估计患者预后及术后治疗的生物学指标。     

视黄酸在体内外对胃癌细胞转移及其相关蛋白的影响

目的:从体内外探讨全反式视黄酸(ATRA)对人胃癌细胞转移及其相关蛋白影响.方法:胃癌细胞接种到裸鼠脾包膜,每隔两天灌胃给予ATRA 0.7 mg/kg,6周后处死裸鼠,取出所有在脾和肝形成的肿瘤,一些肿瘤被固定和包埋,另一些肿瘤保存在液氮中用于后续实验.用蛋白质印迹法测定蛋白水平;通过免疫组化显示微血管;采用粘附实验测定细胞粘附能力.结果:ATRA灌胃后,脾移植瘤和肝转移瘤受到明显抑制(50％),血管生成也受到抑制.尽管ATRA在体内外调节nm23和mts1/p16蛋白的方式不同,但高比值的nm23:mtsl/p16与低粘附性相关.ATRA在体内外诱导ICAM-1蛋白表达.结论:ATRA显著抑制移植瘤生长及其向肝转移,这一过程可能与对转移相关蛋白nm23,mstl/p16和ICAM-1的调控有关.     

Tumor-stroma: In vivo assays and intravital imaging to study cell migration and metastasis

The development of metastatic disease is often correlated with poor patient outcome in a variety of different cancers. The metastatic cascade is a complex, multistep process that involves the growth of the primary tumor and angiogenesis, invasion into the local environment, intravasation into the vasculature, tumor cell survival in the circulation, extravasation from the vasculature and sustained growth at secondary organ sites to form metastases. Although in vitro assays of single cell types can provide information regarding cell autonomous mechanisms contributing to metastasis, the in vivo microenvironment entails a network of interactions between cells which is also important. Insight into the mechanisms underlying tumor cell migration, invasion and metastasis in vivo has been aided by development of multiphoton microscopy and in vivo assays, which we will review here.     

LyP-1 modification to enhance delivery of artemisinin or fluorescent probe loaded polymeric micelles to highly metastatic tumor and its lymphatics

Metastatic cancers are prone to form metastasis at a distance and acquire drug resistance, which are very common clinically and major obstacles to successful chemotherapy. Besides the tumor itself, the lymphatic system is increasingly emerging as a new target for anticancer therapy because it is an important route of tumor metastasis. To specifically deliver drug to both highly metastatic tumor and its lymphatics, tumor- and tumor lymphatics-homing peptide (LyP-1) conjugated PEG-PCL micelles (LyP-1-PM) were first constructed. Artemisinin (ART), a natural product with potential anticancer and antilymphangiogenesis effects, was chosen as the model drug and associated into the micelles. Both PM and LyP-1-PM had similar physiochemical properties, about 30 nm in size with uniform distribution. Highly metastatic breast cancer MDA-MB-435S cells and lymphatic endothelial cells (LEC) were applied as cell models. Flow cytometry and confocal microscopy studies showed that LyP-1-PM exhibited its specificity to both cell lines evidenced by its higher cellular uptake than PM. LyP-1-PM-ART demonstrated higher inhibition effect than PM-ART against these two cell lines in cell apoptosis, cell cycle and cytotoxicity tests. Near-infrared imaging showed that LyP-1-PM was distributed more in orthotopic MDA-MB-435S tumor than PM. Further study by colocalization indicated that PM accumulated near blood vessels, while LyP-1-PM further homed to tumor lymphatic vessels. LyP-1-PM achieved higher antitumor efficacy than other ART formulations in vivo with low toxicity. Both in vitro and in vivo studies here proved that LyP-1 modification enhanced the specific delivery of ART or fluorescent probe loaded polymeric micelles to MDA-MB-435S and LEC. Therefore, LyP-1-PM might be promising in terms of specific delivery of therapeutic or imaging agents to both highly metastatic breast tumor and its lymphatics.