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1.
三氧化二砷治疗Scid小鼠鼻咽癌移植瘤的初步实验研究 总被引:4,自引:0,他引:4
目的:研究三氧化二砷(As2O3)对人鼻咽癌小鼠移植瘤的抑制作用。方法:以人鼻咽癌细胞株CSNE-1为研究对象,观察腹腔注射As2O3对鼻咽癌在Scid小鼠体内生长的抑制作用及其毒副反应。结果:As2O3腹腔注射1mg/kg和5mg/kg均能在小鼠体内诱导鼻咽癌细胞凋亡。在5mg/kg剂量组,凋亡诱导最明显且能诱导鼻咽癌细胞分化,并有显著的抑制肿瘤生长作用,抑瘤率为70%,上述剂量对小鼠外周血白细胞无抑制作用,但病理组织学检查显示对肝脏和心脏有轻度毒性,10mg/kg迅速致实验鼠中毒死亡。结论:砷剂在Scid小鼠体内治疗人鼻咽癌移植瘤有效,但存在最适剂量问题,诱导凋亡和分化可能是其抑瘤机制。 相似文献
2.
目的:研究治疗性HPV16Z-Hsp65-E6/E7无佐剂重组蛋白疫苗的抗肿瘤活性。方法:通过淋巴细胞增殖实验和细胞毒性杀伤实验研究该疫苗激发的细胞免疫反应及反应强度;观察该疫苗对小鼠TC-1肿瘤细胞移植瘤的体内治疗作用和对小鼠生存期的影响。结果:重组蛋白疫苗免疫小鼠后,小鼠脾淋巴细胞与该疫苗体外混合培养增殖明显,并可特异性地在体外杀伤TC-1细胞;体内抑瘤试验显示该疫苗对HPV16病毒转化的TC-1细胞小鼠移植瘤的生长有显著的抑制作用。结论:该疫苗能激发特异性细胞免疫反应;显著抑制HPV16转化的TC-1肿瘤细胞生长。 相似文献
3.
将S180腹水癌细胞接种于实验感染约氏疟原虫的小鼠体内,观察疟原虫感染鼠对肿瘤生长的影响。结果表明,感染鼠接种瘤细胞后通过体重和腹围的测量显示腹水的增加速度与对照鼠相比明显减慢,平均生存时间亦明显延长,其生存延长率比对照鼠增加55.6%~235.6%,说明疟原虫感染后小鼠对体内肿瘤的生长具有明显的抑制作用。 相似文献
4.
目的 探讨过氧化酶体增生物激活受体γ(PPARγ)配体罗格列酮对小鼠体内人类胃癌MGC803细胞移植瘤生长的影响.方法 建立人类胃癌MGC803细胞小鼠肾囊膜下移植瘤模型,通过解剖显微镜和HE染色观察50 mg/kg的罗格列酮连续灌胃5 d作用于荷瘤小鼠后对移植瘤生长的抑制作用.结果 50 mg/kg的罗格列酮能明显抑N4,鼠肾囊膜下移植瘤MGC803细胞增生、诱导肿瘤细胞凋亡而抑制移植瘤的生长,抑瘤率达62.9%.结论 PPARγ配体罗格列酮能抑制小鼠体内肾囊膜下MGC803细胞移植瘤生长. 相似文献
5.
目的: 探究白术多糖(polysaccharide of atractylodes macrocephala, PAM)对小鼠结肠癌细胞移植瘤生长的抑制作用及其机制。方法:将荧光酶标记的1×107个结肠癌细胞(HT-29)注射到小鼠结肠浆膜层,建立结肠癌细胞原位移植瘤模型小鼠。待瘤体积达到约230 mm3时,小鼠采用连续10 d 灌胃给药30 mg/kg PAM(PAM组)或生理盐水(对照组);通过肿瘤活体成像技术检测PAM对小鼠体内结肠癌细胞生长的影响,通过流式细胞术检测PAM对瘤体组织中粒细胞、树突状细胞以及巨噬细胞的MHCII以及IL-12 的表达、淋巴细胞的激活以及CD4+和CD8+细胞分泌IFN-γ 功能的影响。结果:PAM可显著抑制结肠癌原位移植瘤模型小鼠体内结肠癌细胞生长(P<0.01)。PAM可通过增加MHCII 和IL-12 在树突状细胞和巨噬细胞中的表达水平(均P<0.01),PAM可显著增加瘤体组织中CD8+细胞、NK细胞、CD44+/NK细胞和CD44+/CD4+细胞比例以及提升单位组织体积中CD8+细胞和NK细胞细胞数量(均P<0.01),PAM可显著增加CD4+及CD8+细胞分泌IFN-γ 的能力(均P<0.01)。结论:PAM可通过激活结肠癌模型小鼠原位移植瘤组织中免疫细胞来抑制肿瘤生长。 相似文献
6.
百福生胶囊对荷瘤小鼠的抗肿瘤作用研究 总被引:2,自引:0,他引:2
目的:探讨百福生胶囊对荷瘤小鼠体内和体外的抗肿瘤机理。方法:体内抑瘤实验,分别对肉瘤S180和H22腹水肝癌小鼠模型灌胃给药后取瘤称重,计算抑瘤率判断百福生胶囊对两种瘤体的抑制作用,生存期实验;荷瘤小鼠接种癌细胞后24hr开始灌胃给药,10天于每3天给药一3次,比较洛组小鼠存活时间;体外抑瘤实验,用体外培养法研究百福生胶囊对人宫颈部Hela细胞生长的抑制作用。结果:百福生胶囊对两种实体瘤均有显的抑制作用,并明显延长荷瘤小鼠的存活天数,同时,该产品可有效抑制Hela细胞的生长。 相似文献
7.
《中国医学文摘:肿瘤学》2006,20(4):306-311
AZT对肝癌细胞端粒酶活性及相关蛋白表达的影响;RNA干扰SMYD3基因衰达对诱导肝癌细胞凋亡的影响;血管内皮生长因子和基质金属蛋白酶-2在肝细胞肝癌中的表达殛临床意义;肝细胞生长因子对卵巢癌细胞侵袭的促进作用及信号转导途径;环氧合酶-2抑制剂塞米昔布对人肝癌HepG2裸小鼠移植瘤生长和肿瘤血管生成的抑制作用。 相似文献
8.
目的 :研究三氧化二砷 (As2 O3)对人鼻咽癌小鼠移植瘤的抑制作用。方法 :以人鼻咽癌细胞株CSNE 1为研究对象 ,观察腹腔注射As2 O3对鼻咽癌在Scid小鼠体内生长的抑制作用及其毒副反应。结果 :As2 O3腹腔注射 1mg/kg和 5mg/kg均能在小鼠体内诱导鼻咽癌细胞凋亡。在 5mg/kg剂量组 ,凋亡诱导最明显且能诱导鼻咽癌细胞分化 ,并有显著的抑制肿瘤生长作用 ,抑瘤率为 70 %。上述剂量对小鼠外周血白细胞无抑制作用 ,但病理组织学检查显示对肝脏和心脏有轻度毒性。 10mg/kg迅速致实验鼠中毒死亡。结论 :砷剂在Scid小鼠体内治疗人鼻咽癌移植瘤有效 ,但存在最适剂量问题 ,诱导调亡和分化可能是其抑瘤机制 相似文献
9.
三氧化二砷的抗大肠癌作用及其机制 总被引:2,自引:0,他引:2
Wang XS Wang GY Xu HT Wang K Liu M Fu SB Geng JS Zhang QF Dong XS Zhao JH 《中华肿瘤杂志》2007,29(6):415-418
目的观察三氧化二砷(As2O3)对大肠癌LS-174T细胞生长及端粒酶活性的影响。方法As2O3作用于大肠癌LS-174T细胞和裸鼠移植瘤后,采用噻唑盐(MTT)比色法检测结肠癌细胞生长抑制情况,电镜检测细胞超微结构的改变,荧光染色观察细胞核形态变化,流式细胞术(FCM)检测As2O3对细胞周期的影响,聚合酶链反应-酶联免疫反应(PCR-ELISA)试剂盒检测细胞中端粒酶活性变化。结果MTT法显示,随着As2O3浓度的升高,LS-174T细胞存活率明显下降,IC50= 5.23μmol/L。As2O3作用于LS-174T细胞24 h即出现凋亡峰,凋亡细胞的数量随着作用时间增加而增加。As2O3对LS-174T细胞提取液端粒酶活性有一定的抑制作用,对癌细胞端粒酶活性抑制作用随作用时间的延长而加强。从实验动物瘤体积和瘤重两个指标分析,As2O3组与对照组相比具有明显的抑癌作用(P<0.05)。结论经体外、体内实验证实,As2O3对结肠癌LS-174T细胞生长和裸鼠移植瘤均有抑制作用,其抗癌机制可能与诱导细胞凋亡和抑制端粒酶活性有关。 相似文献
10.
11.
Hua Guo Menghui Li Peng Chen David J. Blake Xiaoni KongXishan Hao Ruifang Niu Ning Zhang 《Cancer letters》2011
Metastasis remains a formidable problem in malignant tumors. In this study, MTT assay revealed that 4-methyl-3-nitro-benzoic acid (MNBA) had no effect on cell viability and did not interfere with cell cycle in any breast cancer cell lines tested. However, treatment with MNBA on breast cancer cells can inhibit EGF-induced migration and chemotaxis in vitro. In vivo assay demonstrated that MNBA and Paclitaxel synergistically inhibited tumor growth and metastasis in breast cancer SCID mice xenografts. These results suggest that MNBA is a potent inhibitor cancer cell chemotaxis and may be developed into a novel anti-metastasis drug. 相似文献
12.
Hafner C Breiteneder H Ferrone S Thallinger C Wagner S Schmidt WM Jasinska J Kundi M Wolff K Zielinski CC Scheiner O Wiedermann U Pehamberger H 《International journal of cancer. Journal international du cancer》2005,114(3):426-432
The lack of efficacy of available therapies for the treatment of malignant melanoma has emphasized the need to develop novel therapeutic strategies to prevent melanoma growth. We have tested whether the anti-HMW-MAA mAb 225.28S is able to inhibit human melanoma tumor growth in SCID mice because in vitro data suggested that this antigen plays a role in spreading, migration and invasion of melanoma cells. Tumors were established by subcutaneous injection of the human melanoma cell line 518A2 into SCID mice. When tumors reached a size of 5 mm, the mAb 225.28S was administered intravenously 4 times in 3 day intervals at 100 microg/injection. Within 14 days after the first administration of the mAb 225.28S, tumor growth was reduced by 52% as compared to control mice. Three hundred and seven genes of >20,000 genes contained on the GeneChip were changed in their expression level at least 2-fold after administration of the mAb 225.28S. The encoded proteins were mostly components or modifiers of the extracellular matrix, tumor suppressors, and melanogenesis associated proteins. Surprisingly, the administration of the control mAb that did not lead to a significant tumor growth inhibition in vivo resulted in the modulation of two-thirds of these genes. This is the first report of suppression of human melanoma tumor growth in SCID mice by the mAb 225.28S. Our results suggest that anti-HMW-MAA mAbs may represent useful reagents to apply passive immunotherapy to patients with malignant melanoma. 相似文献
13.
Ta-Chiang Liu Tingguo Zhang Hiroshi Fukuhara Toshihiko Kuroda Tomoki Todo Xavier Canron Andreas Bikfalvi Robert L Martuza Andreas Kurtz Samuel D Rabkin 《Clinical cancer research》2006,12(22):6791-6799
PURPOSE: Oncolytic herpes simplex viruses (HSV) appear to be a promising platform for cancer therapy. However, efficacy as single agents has thus far been unsatisfactory. Fibroblast growth factor (FGF) signaling is important for the growth and migration of endothelial and tumor cells. Here, we examine the strategy of arming oncolytic HSV with a dominant-negative FGF receptor (dnFGFR) that targets the FGF signaling pathway. EXPERIMENTAL DESIGN: A mouse Nf1:p53 malignant peripheral nerve sheath tumor (MPNST) cell line expressing dnFGFR was generated by transfection. The effects of dnFGFR expression on cell growth and migration in vitro and tumor formation in vivo were determined. The dnFGFR transgene was then inserted into oncolytic HSV G47Delta using a bacterial artificial chromosome construction system. Antitumoral and antiangiogenic activities of bG47Delta-dnFGFR were examined. RESULTS: MPNST 61E4 cells expressing dnFGFR grew less well than parental control cells. bG47Delta-dnFGFR showed enhanced killing of both tumor (human U87 glioma and F5 malignant meningioma cells and murine MPNST 61E4 and 37-3-18-4 cells) and proliferating endothelial cells (human umbilical vascular endothelial cell and Py-4-1) in vitro compared with the control vector bG47Delta-empty without inhibiting viral replication. In vivo, bG47Delta-dnFGFR was more efficacious than its nonexpressing parent bG47Delta-empty at inhibiting tumor growth and angiogenesis in both human U87 glioma and mouse 37-3-18-4 MPNST tumors in nude mice. CONCLUSIONS: By using multiple therapeutic mechanisms, including destruction of both tumor cells and tumor endothelial cells, an oncolytic HSV encoding dnFGFR enhances antitumor efficacy. This strategy can be applied to other oncolytic viruses and for clinical translation. 相似文献
14.
Lonnroth C Svaninger G Gelin J Cahlin C Iresjo B Cvetkovska E Edstrom S Andersson M Svanberg E Lundholm K 《International journal of oncology》1995,7(6):1405-1413
Tumor-bearing mice with two different locally growing malignant tumors (epithelial like, MCG 101; malignant melanoma, K1735-M2) were used to evaluate the putative role of prostaglandins for survival and local tumor growth in experimental cancer. Daily systemic injections of indomethacin (1 mu g/g bw) were used to block prostaglandin production in normal and T-cell deficient tumor-bearing nude mice. Tumor progression was determined by measurements of tumor weight, DNA-synthesis, cell cycle kinetics in vivo and in vitro (flow cytometry), tumor tissue concentrations of polyamines (putrescine, spermidine, spermine) and tumor tissue gene expression of growth regulating factors (IL-1 alpha, IL-6, TNF alpha, A,B-PDGF, EGF, VEGF, bFGF, TGF beta(3), angiogenin and transferrin receptor). Tumor tissue content of von Willebrandt factor VIII was estimated by immunohistochemistry. Indomethacin had no effect on survival, host nutritional state or local tumor growth in mice bearing the malignant melanoma with low PGE(2) production. In contrast, indomethacin prolonged survival, improved cachexia and decreased tumor growth in mice bearing the MCG 101 tumor with hundredfold higher prostaglandin tumor production, leading to elevated liver and muscle tissue as well as plasma concentrations of PGE(2). Indomethacin inhibited almost completely the high tumor PGE(2) production in MCG tumors, leading to prolonged potential doubling time for tumor growth in vivo, and a trend to decreased tumor tissue concentration of polyamines (spermidine). Indomethacin had no inhibitory effect on tumor cell proliferation in vitro, although PGE(2) production was decreased by 75%. The effect of indomethacin in vivo was independent of T-cells and was observed with similar magnitude irrespective of the number of MCG cells (10(4)-10(6)) implanted or the site of implantation (s.c., i.p., liver, lung, skeletal muscles). Tumor growth inhibition by indomethacin was not intrinsically transferable by tumor cells from indomethacin treated tumor-animals. Tumor expression of mRNA for several growth regulating factors were either increased (IL-6, TNF alpha, GM-CSF, TGF beta(3)) unchanged (EGF, VEGF, PDGF A,B, IL-1 alpha, transferrin receptor) or decreased (b-FGF and angiogenin) (p<0.05) by indomethacin treatment of MCG mice. Decreased tumor content of von Willebrandt factor VIII in combination with an attenuated tumor vasculature were associated with decreased tumor growth (p<0.05). Our results confirm that high tumor production of prostaglandins was related to reduced survival. Tumor prostaglandins probably promote local tumor growth by stimulation of tumor surrounding cells to produce growth factor(s) for tumor angiogenesis including tumor and matrix cell proliferation unrelated to immune cells. 相似文献
15.
目的:观察温阳散结汤对 Lewis 肺癌小鼠肿瘤生长及瘤组织中巨噬细胞M2型极化的影响,并探索其调控NF-κB信号通路抑制肿瘤相关巨噬细胞M2型极化,对Lewis肺癌细胞侵袭、迁移能力的影响。方法:建立C57BL/6小鼠 Lewis 肺癌移植瘤模型,温阳散结汤干预14 d 后观察小鼠瘤重和肺转移灶,计算肺转移抑瘤率,免疫组化染色检测小鼠瘤组织中巨噬细胞M2型表面标志物 CD206 的表达;温阳散结汤灌胃SD大鼠制备含药血清,采用IL-13干预RAW264.7小鼠巨噬细胞建立巨噬细胞M2型极化模型,CCK-8法检测温阳散结汤含药血清对巨噬细胞增殖的影响,流式细胞术和Western-blot检测 CD206的表达,RT-PCR检测巨噬细胞M2型标志基因的mRNA表达,ELISA法检测细胞上清中IL-1β、IL-10、TGF-β 和TNF-α 的水平变化,Western-blot检测氧化物酶体增殖物激活受体γ(PPARγ)、核因子-κB p65(NF-κB p65)和磷酸化核因子-κB p65(pNF-κB p65)的蛋白表达;收集温阳散结汤含药血清处理的M2型巨噬细胞条件培养基,将其作用于Lewis肺癌细胞,通过Transwell侵袭迁移实验检测Lewis 肺癌细胞的侵袭和运动迁移能力。结果:温阳散结汤干预后,明显减少了小鼠瘤重和肺转移灶数,并抑制了瘤组织CD206的阳性表达(P<0.05);温阳散结汤含药血清干预后,IL-13诱导的M2型巨噬细胞中F4/80+CD206+的细胞比例和CD206蛋白表达明显减少,MRC1、Arg1、Ym1的mRNA表达水平显著降低,细胞中TNF-α、IL-1β的含量明显升高,IL-10、TGF-β的含量明显降低,同时明显下调了细胞PPARγ、NF-κB p65、pNF-κB p65的蛋白表达及pNF-κB p65/NF-κB p65比值(均P<0.05);温阳散结汤含药血清处理的M2型巨噬细胞条件培养基干预后,Lewis肺癌细胞迁移和侵袭细胞数明显减少(P<0.05)。结论:温阳散结汤具有抑制肺癌肿瘤生长和转移的作用,其作用机制可能与调节NF-κB通路,抑制IL-13诱导的RAW264.7细胞M2型极化,从而抑制Lewis肺癌细胞侵袭和迁移能力相关。 相似文献
16.
Megumi Miyamoto Yuki Kawato Ryonosuke Fujie Kaoru Kurowarabe Kakeru Fujiwara Reika Nobusawa Ryota Hayashi Kei Iida Izumi Ohigashi Haruko Hayasaka 《Cancer science》2023,114(9):3509-3522
CCL21-Ser, a chemokine encoded by the Ccl21a gene, is constitutively expressed in the thymic epithelial cells and stromal cells of secondary lymphoid organs. It regulates immune cell migration and survival through its receptor CCR7. Herein, using CCL21-Ser-expressing melanoma cells and the Ccl21a-deficient mice, we demonstrated the functional role of cancer cell-derived CCL21-Ser in melanoma growth in vivo. The B16-F10 tumor growth was significantly decreased in Ccl21a-deficient mice compared with that in wild-type mice, indicating that host-derived CCL21-Ser contributes to melanoma proliferation in vivo. In Ccl21a-deficient mice, tumor growth of melanoma cells expressing CCL21-Ser was significantly enhanced, suggesting that CCL21-Ser from melanoma cells promotes tumor growth in the absence of host-derived CCL21-Ser. The increase in tumor growth was associated with an increase in the CCR7+ CD62L+ T cell frequency in the tumor tissue but was inversely correlated with Treg frequency, suggesting that naïve T cells primarily promote tumor growth. Adoptive transfer experiments demonstrated that naïve T cells are preferentially recruited from the blood into tumors with melanoma cell-derived CCL21-Ser expression. These results suggest that CCL21-Ser from melanoma cells promotes the infiltration of CCR7+ naïve T cells into the tumor tissues and creates a tumor microenvironment favorable for melanoma growth. 相似文献
17.
Serra M Miquel L Domenzain C Docampo MJ Fabra A Wight TN Bassols A 《International journal of cancer. Journal international du cancer》2005,114(6):879-886
Versican is a large chondroitin sulfate proteoglycan produced by several tumor cell types, including malignant melanoma. The expression of increased amounts of versican in the extracellular matrix may play a role in tumor cell growth, adhesion and migration. We have expressed the V3 isoform of versican in human and canine melanoma cell lines. Retroviral overexpression of V3 did not change the morphology of any of the cell lines but markedly reduces cell growth in the V3 versican expressing melanoma cells. The V3-overexpressing melanoma cells retain their diminished growth potential in vivo because primary tumors arising from these cell lines growth more slowly than their vector only counterparts. This effect was accompanied by increases in cell adhesion on hyaluronan and an enhanced ability to migrate on hyaluronan-coated transwell chambers. This enhanced migration is blocked when cells are preincubated with soluble hyaluronan, or anti-CD44 antibodies, suggesting that V3 acts by altering the hyaluronan-CD44 interaction. Hyaluronan content and CD44 expression are not altered in V3-overexpressing cells compared to vector-transduced cells. Our results show that V3 overproduction modulates the in vitro behavior of human and canine melanoma cell lines and reduces their tumorigenicity in vivo. 相似文献
18.
Sonoda S Tachibana K Uchino E Yamashita T Sakoda K Sonoda KH Hisatomi T Izumi Y Sakamoto T 《Cancer biology & therapy》2007,6(8):1276-1283
Ultrasound exposure-induced cavitation has been shown to accentuate cell membrane permeability, thus promoting effective drug delivery into cells, a technique that can be enhanced in the presence of microbubbles (MB). Here we applied this method as a treatment for malignant melanoma of the eyelid. The incidence of malignant melanoma in ophthalmology is relatively high, but its treatment is cosmetically difficult. A greater in vitro growth suppression of B-16 melanoma cells was achieved using ultrasound and MB in combination with the anticancer drug bleomycin than when a more concentrated dose of bleomycin alone was applied to the cell culture. Moreover, this effect was enhanced in an in vivo tumor model created by injecting B-16 melanoma cells into the lower eyelids of SCID mice. The antitumor effect of bleomycin was observed at a lower dose (0.5 mg/ ml) when the treatment was used in conjunction with ultrasound. The effect was further enhanced when MB were included, with tumor shrinkage occurring at bleomycin levels of 0.06 mg/ml. These results show that ultrasound and MB promote efficient bleomycin uptake by cells, and that the technique is a potentially useful drug delivery method. 相似文献
19.
Rouleau C Menon K Boutin P Guyre C Yoshida H Kataoka S Perricone M Shankara S Frankel AE Duesbery NS Vande Woude G Biemann HP Teicher BA 《International journal of oncology》2008,32(4):739-748
Two of the three components of anthrax toxin, protective antigen (PA) and lethal factor (LF), together known as lethal toxin (LeTx), reportedly show anti-tumor activity in melanoma in vitro and in vivo. The growth inhibitory activity of LeTx in culture was determined in nine human cancer cell lines, including melanoma, neuroblastoma and adenocarcinoma cells, as well as in human umbilical vein endothelial cells (HUVEC). The contribution of the two known PA receptor proteins, ANTXR1/TEM8 and ANTXR2/CMG2, to the sensitivity of the cells was assessed. The efficacy of LeTx was evaluated in vivo in the SK-N-AS neuroblastoma and SK-MEL-28 melanoma tumor xenograft models. Sensitivity to LeTx in vitro was observed in the neuroblastoma and colorectal adenocarcinoma cells and HUVEC, as well as melanoma cells. ANTXR1/TEM8 and ANTXR2/CMG2 protein expression studies suggested that a certain threshold of the PA receptor protein level must be met for sensitivity to LeTx to be observed. However, although the SK-N-AS neuroblastoma cells expressed the highest levels of receptor proteins and achieved the lowest IC50 in vitro (0.1 ng/ml), we observed no correlation between either the ANTXR1/TEM8 or ANTXR2/CMG2 protein levels and sensitivity to LeTx in vitro. In vivo, LeTx was an active anti-tumor agent when administered intravenously to mice bearing the human SK-N-AS or SK-MEL-28 tumor xenografts. The tumor growth delays were 6-8 days with a lower dose regimen and 14-16 days with a higher dose regimen for the two tumor models. These in vitro data suggest that LeTx may have broad therapeutic indications in cancer and the in vivo studies demonstrate that LeTx has systemic efficacy in neuroblastoma as well as melanoma. The therapeutic potential of LeTx needs to be further investigated in non-melanoma tumor models expressing the ANTXR1/TEM8 and/or ANTXR2/CMG2 protein. 相似文献
20.
Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine 总被引:5,自引:0,他引:5
Swainsonine, an inhibitor of alpha-mannosidases, has been shown to block experimental metastasis of B16F10 melanoma and MDAY-D2 lymphoid tumor cells in syngeneic mice. In this report we demonstrate that swainsonine also reduces the growth rate of human melanoma cells in vitro and in vivo. Graded doses of swainsonine were administered either orally or via implanted Alzet miniosmotic pumps to athymic nude mice bearing subcutaneously implanted human MeWo melanoma cells. Swainsonine at 10 micrograms/ml in the drinking water or 0.5 mg/kg/day administered by miniosmotic pump reduced the growth rate of the MeWo tumors by approximately 50% and inhibited the expression of complex-type oligosaccharides in tumors and host intestine by only 10-20%. Swainsonine doses of 4 mg/kg/day reduced expression of complex-type oligosaccharides by 85% in vivo but afforded no additional inhibitory effect. A glycosylation mutant of MeWo called 3S5 has a defect in the synthesis of complex-type asparagine-linked oligosaccharides resulting in incomplete processing similar to that observed in swainsonine-treated MeWo tumor cells. Swainsonine did not inhibit the proliferation of 3S5 cells in vitro nor the growth of 3S5 tumors in nude mice. The results suggest that expression of highly branched complex-type oligosaccharides commonly associated with the malignant phenotype may provide the tumor cells with a growth advantage. 相似文献