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。     

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。     

鸦胆子油乳对小鼠黑色素瘤高转移细胞黏附、侵袭及转移能力的影响

目的研究鸦胆子油乳对B16-BL6小鼠高转移细胞黏附、侵袭及转移能力的影响.方法采用细胞黏附实验、重组基底膜侵袭实验以及小鼠黑色素瘤自发性转移模型,观察鸦胆子油乳对B16-BL6细胞黏附、侵袭及转移能力的影响.结果在3和6μL·mL-1浓度时,鸦胆子油乳与B16-BL6细胞作用24h,可抑制其与纤粘连蛋白的黏附,抑制率分别为24.5%和63.2%;也抑制其与层粘连蛋白的黏附,抑制率分别为17.0%和34.5%;对B16-BL6细胞侵袭重组基底膜的抑制率为26.7%和41.3%.在小鼠黑色素瘤自发性转移模型中,鸦胆子油乳2.5,5.0,10.0mL·kg-1连续注射给药1个月,小鼠肺转移灶与对照组相比明显减少.结论鸦胆子油乳具有抑制B16-BL6细胞黏附、侵袭及转移的作用.     

YIGSR聚合衍生物对B16黑色素瘤细胞实验性肺转移的抑制作用

目的 :研究Tyr-Ile-Gly-Ser-Arg(YIGSR )均叉、杂叉聚合肽的抗肿瘤转移作用。方法 :观察药物对B16黑色素瘤细胞实验性肺转移的影响。结果 :尾静脉接种B16黑色素瘤细胞第21天 ,46例对照组和实验组小鼠肺转移瘤灶形成比例100 %。10例对照组小鼠平均肺转移结节数105 5±78 2。与瘤细胞共注射的适宜剂量YIGSR均叉、杂叉肽可明显降低实验组小鼠的肺转移结节数 ,并呈一定的剂量依赖关系。其中 ,100μg～200μgYIGSR均叉和同剂量杂叉肽组肺转移结节数与对照组比较 ,P<0.05和P<0.01 ;50μg均叉肽与对照组比较 ,P<0.05。但受试合成肽未明显降低已形成肺转移小鼠的肺脏重量。结论 :YIGSR聚合衍生物有较强的抗肿瘤转移作用 ,其机制与瘤细胞栓塞、滞留于远隔靶器官的微血管中并增殖 ,瘤细胞穿出血管或淋巴管 ,在靶器官内形成微转移灶有关     

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。     

五味子多糖对S180荷瘤小鼠红细胞免疫抗肿瘤的作用

目的:探讨五味子多糖(FSCP)增强荷瘤小鼠红细胞结构稳定性与红细胞免疫黏附功能的抗肿瘤作用及其红细胞免疫调节机制。方法:实验动物随机分为正常对照组、生理盐水组、环磷酰胺(CP)组及FSCP高、中、低3个剂量组。用药7d后,眼球取血,获得红细胞悬液。采用激光共聚焦技术检测荷瘤小鼠红细胞Ca2+含量的变化;采用分光光度法检测红细胞膜唾液酸(SA)含量、红细胞膜封闭度;采用荧光偏振法检测红细胞膜脂流动性(LFU);采用花环法检测红细胞天然免疫黏附能力。结果:与生理盐水组比较,FSCP各组能降低荷瘤小鼠红细胞Ca2+的浓度(P<0.01),增加红细胞膜表面SA含量(P<0.01)以及红细胞膜自我封闭度(P<0.05或P<0.01)。高剂量FSCP可提高S180荷瘤小鼠红细胞膜流动性(P<0.05);增强S180荷瘤小鼠红细胞免疫黏附肿瘤细胞的能力(P<0.05),FSCP高剂量组免疫花环率达到24.17%。结论:FSCP可能通过改善S180荷瘤小鼠红细胞膜的功能状态,提高膜的稳定性,增强红细胞免疫黏附肿瘤细胞的能力,从而发挥其抗肿瘤作用。     

川芎嗪抗肿瘤转移作用及其机理

川芎嗪(TTMP)在20mg·kg~(-1)·d~(-1)剂量下,给药18d,能显著抑制B16-F10黑素瘤的人工肺转移,其肺转移结节数由134个下降到72个.放射免疫法测定TTMP能显著降低肺转移小鼠血浆TXB_2含量,而对6-keto-PGF_(1α)含量无显著影响.同位素参入法测定TTMP能增强正常及荷瘤小鼠脾脏NK细胞活性,且能拮抗环磷酰胺对NK细胞活性的抑制作用.TTMP抗肿瘤转移作用可能与降低小鼠血浆TXB_2含量和增强NK细胞活性有关     

桔梗根的水提取物对肿瘤侵润和转移的抑制作用

目的 通过研究桔梗根水提取物对肿瘤细胞的影响机制,探讨对肿瘤侵润和转移的抑制作用.方法 应用经改良的在Transwell细胞培养真空箱中进行的肿瘤细胞体外侵润分析法和实验性肺转移体内测定与自然杀伤细胞活性试验,进行统计学分析. 结果 桔梗根水提取物所含CK对侵润重建基底膜(基质胶)的B16-F10细胞有抑制作用.CK抑制B16-F10细胞侵润基质胶/纤维结合蛋白-包埋过滤膜的作用呈现浓度依赖方式.结论 CK在肿瘤细胞侵润方面的作用具有高侵润和转移能力,为改善肿瘤侵润和寻找转移治疗方法 提供了参考.     

海参岩藻聚糖硫酸酯抑制小鼠肿瘤生长和转移及其作用机制的研究

目的探讨海参岩藻聚糖硫酸酯(sea cucumber fu-coidan,SC-FUC)对小鼠肿瘤生长和转移的抑制作用及其机制。方法建立C57 BL/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法检测肿瘤组织中缺氧诱导因子(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、乙酰肝素酶(heparanase,HPA)和基质金属蛋白酶-2/9(matrix metalloproteinase-2/9,MMP-2/9)mRNA的表达。结果 SC-FUC可以抑制荷瘤小鼠肿瘤的生长,其平均抑制率为45.5%,并可以减少肺表面转移灶结节数(P<0.01),平均抑制率为66.0%。SC-FUC可以降低荷瘤小鼠肿瘤组织中HIF-1α、VEGF、HPA、MMP-2/9 mRNA的表达(P<0.05,P<0.01)。结论 SC-FUC能抑制肿瘤细胞在小鼠体内的生长和转移,其机制可能与抑制肿瘤血管新生,降低肿瘤细胞的迁移能力有关。     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。     

岩藻糖基化海参硫酸软骨素抑制肿瘤血管新生作用的研究

目的从美国肉参(Isostichopus badionotus)中分离纯化岩藻糖基化海参硫酸软骨素(sea cucumber chondroitin sulfate,SC-CHS),体外研究其对肿瘤诱导血管生成的抑制作用。方法采用MTT法检测SC-CHS对95D细胞增殖活性的影响;小管形成实验研究SC-CHS对脐静脉内皮细胞(HUVEC)小管形成能力的抑制作用;采用鸡胚尿囊膜(CAM)新生血管模型,研究其对血管生成的影响;通过RT-PCR和WesternBlot法检测其对肿瘤诱导血管生成相关因子缺氧诱导因子(hypoxia inducible factor-1α,Hif-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA和蛋白的表达。结果结果显示SC-CHS能显著抑制95D细胞的增殖,能抑制HUVEC的小管形成作用和CAM血管新生。RT-PCR和Western Blot检测结果表明,高剂量SC-CHS能显著降低95D细胞中Hif-1α和VEGF mRNA的表达,减少VEGF蛋白的合成。结论SC-CHS体外能显著抑制肿瘤血管生成,这可能是通过影响肿瘤细胞中VEGF的合成发挥作用。     

Capsaicin induced apoptosis of B16-F10 melanoma cells through down-regulation of Bcl-2.

Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a pungent ingredient of hot chili peppers, has been reported to possess substantial anticarcinogenic and antimutagenic activities. In the present study, we investigated the effect of capsaicin on induction of apoptosis in highly metastatic B16-F10 murine melanoma cells. Capsaicin inhibited growth of B16-F10 cells in a concentration-dependent manner. Proapoptotic effect of capsaicin was evidenced by nuclear condensation, internucleosomal DNA fragmentation, in situ terminal nick-end labeling of fragmented DNA (TUNEL), and an increased sub G1 fraction. Treatment of B16-F10 cells with capsaicin caused release of mitochondrial cytochrome c, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase in a dose-dependent manner. Furthermore, Bcl-2 expression in the B16-F10 cells was slightly down-regulated by capsaicin treatment. In contrast, there were no alterations in the levels of Bax in capsaicin-treated cells. Collectively, these findings indicate that capsaicin-induces apoptosis of B16-F10 melanoma cells via down-regulation the Bcl-2.     

Enhancement of nk cytotoxicity,antimetastasis and elongation effect of survival time in b16-f10 melanoma cells by oregonin

We investigated the antitumor activity of oregonin, a diarylheptanoid derivative purified from Alnus hirsuta Turcz, Betulaceae. Oregonin is a potential novel immunomodulator, which augments the activation of natural killer (NK) cells, and thereby leads to a powerful antitumor activity. To evaluate the cytotoxicity of oregonin against tumor cells, we examined the effectiveness of NK cells and determined that oregonin could increase NK cell cytotoxicity. This was confirmed by MTT assay. In addition, the survival time of C57BL/6 mice were measured by inoculating B16-F10 melanoma cells to mice via intra muscular (i.m.) injection. Oregonin treatment after 10 hours of inoculation at 10 mg/kg dosage showed a significant extension of survival time by up to 51.32%, when compared to the control group. Moreover, oregonin significantly reduced the incidence of pulmonary metastasis, which may be developed from B16-F10 melanoma cells. These findings suggest that oregonin may be classified as a new and novel immunomodulator due to its potential antitumor activity.     

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.     

三肽化合物酪丝亮肽对巨噬细胞吞噬及肿瘤细胞杀伤功能的影响

目的：研究三肽化合物酪丝亮肽(YSL)对巨噬细胞(M(?))吞噬功能、肿瘤细胞杀伤功能和细胞因子分泌功能的影响。方法：通过碳粒廓清实验观察YSL对小鼠M(?)吞噬功能的影响,采用MTT法观察YSL对腹腔M(?)杀伤人肝癌细胞BEL-7402和小鼠黑色素瘤细胞B16-F10作用的影响,用ELISA法观察YSL对M(?)株RAW264．7分泌细胞因子IL-1β和NO功能的影响。结果：YSL 80,160,320μg·kg~(-1)·d~(-1)均能够明显增强小鼠M(?)的吞噬功能(P＜0．01),YSL各浓度(0．1,1,10,100 mg·L~(-1))在体外明显增强小鼠腹腔M(?)对肿瘤细胞BEL-7402和B16-F10的杀伤作用(P＜0．01)。YSL可以促进细胞毒效应分子IL- 1β和NO的分泌合成,NO和IL-1β水平分别在YSL作用12 h,24 h时达到高峰。结论：YSL可以增强M(?)吞噬功能,增强对肿瘤细胞的杀伤作用,促进细胞因子IL-1β和NO分泌。     

Anticancer properties of 10-hydroxycamptothecin in a murine melanoma pulmonary metastasis model in vitro and in vivo

Lung cancer, including lung metastatic cancer, remains one of the most difficult types of cancer to treat. Therefore, the search for new agents for its treatment is very important. 10-Hydroxycamptothecin (HCPT) was proved to have ideal anticancer activity in curing series cancer cells. In this study, the anticancer effect of HCPT on melanoma lung metastasis cancer was investigated by several administration routes, and whether the effect may be attributed to the induction of tumor cells apoptosis was determined. MTT assay results showed that HCPT exhibited selective cytotoxic activity against B16-F10 cells in a concentration- and time-dependent manner. Hoechst 33258 staining and transmission electron microscopy showed typical apoptotic morphology such as condensed chromatin, irregular nuclei, and apoptotic body formation. Flow cytometry analysis indicated a growth on apoptotic cells and a cell-cycle arrest in S phase after treatment with HCPT. In vivo melanoma pulmonary metastases were inhibited by treatment with HCPT. A more significant inhibition was observed if HCPT was administered by aerosol inhalation than that given by i.v. or i.p. administration. Thus, HCPT exhibited potential anticancer activity against B16-F10 cells in vitro and in vivo. However, the possible mechanisms involved still need to be investigated to explain this behavior.     

A cell-based drug delivery system for lung targeting: II. Therapeutic activities on B16-F10 melanoma in mouse lungs

The in vitro and in vivo anticancer activities of doxorubicin-loaded B16-F10 murine melanoma cells (DLTC) were evaluated. DLTC showed similar growth-inhibitory effects against live B16-F10 cells with doxorubicin solution in cell culture system, with the IC₅₀     

A Cell-Based Drug Delivery System for Lung Targeting: II. Therapeutic Activities on B16-F10 Melanoma in Mouse Lungs

The in vitro and in vivo anticancer activities of doxorubicin-loaded B16-F10 murine melanoma cells (DLTC) were evaluated. DLTC showed similar growth-inhibitory effects against live B16-F10 cells with doxorubicin solution in cell culture system, with the IC₅₀     

Antimelanoma activity of 1,3,4-thiadiazolium mesoionics: a structure-activity relationship study

The effect of a series of 4-phenyl-5-(2'-Y, 4'-X or 4'-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chlorides was evaluated against B16-F10 murine melanoma cells in vitro and against tumors resulting from implanted B16-F10 cells in C57BL/6 mice. These compounds differ from each other only at the cinnamoyl ring substituent (MI-J, X=OH; MI-2,4diF, X=Y=F; MI-4F, X=F and MI-D, X=NO2). The results were compared with those obtained for MI-D, which has already been shown to be a potent and promising drug against melanoma. On exposure of B16-F10 cells to MI-D, MI-2,4diF and MI-4F, all of them at the same micromolar concentration (50 microM) decreased the cell viability to 8, 50 and 22%, respectively, while MI-J did not show any significant effect under the same conditions. However, low doses such as 10 microM MI-D were sufficient to impair cell growth over 72 h, but for MI-2,4diF and MI-4F the effect on B16-F10 proliferation was only observed at a concentration of 25 microM. Furthermore, MI-4F had a slightly better effect than MI-2,4diF in vitro; its effect on tumor growth in vivo was not significant. MI-D inhibited tumor growth by 77%. The greater effectiveness of MI-D compared with MI-2,4diF, MI-4F and MI-J against B16-F10 melanoma cells is probably due to its stronger electron-withdrawing group (NO2), which increases the positive charge on the mesoionic ring and allows extensive conjugation of the side-chain with the exocyclic moiety. This seems to be important for degree of anti-tumor activity of these compounds.     

Effects of Cordyceps militaris extract on angiogenesis and tumor growth

INTRODUCTIONAngiogenesis is the process of new blood vesselformation from existing blood vessels and a natural re-sponse of tissues to ischemia[1]. The steps of angio-genesis involve proteolytic degradation of extracelluarmatrix, endothelial cell-matrix adhesion, migration,proliferation, and differentiation[2]. This biological re-action is often associated with some diseases, such assolid tumor[3], diabetic retinopathy[4], and rheumatoidarthritis[5].Tumor formation requires the developm…