期刊文献+

川芎嗪联合顺铂对小鼠Lewis肺癌中Mac2-BP和VEGF表达的影响 被引量:7

Effect of TMP combined with cisplatin on expression of Mac2-BP and VEGF in Lewis lung cancer mice
原文传递
导出
摘要 目的探讨川芎嗪(TMP)联合顺铂(DDP)对小鼠Lewis肺癌Mac2-结合蛋白(Mac2-BP)和血管内皮生长因子(VEGF)表达的影响。方法 C57BL/6小鼠皮下接种Lewis肺腺癌细胞,建立小鼠Lewis肺癌移植瘤模型,40只小鼠随机分为4组:生理盐水组(NS组,0.9%氯化钠,0.2 ml)、TMP组(TMP 100 mg/kg,0.2 ml)、DDP组(DDP2 mg/kg,0.2 ml)、TMP+DDP组(TMP 100 mg/kg,DDP 2 mg/kg;共0.2 ml),每组10只,于接种后14 d给予药物干预,每隔1 d测量瘤体长短径并计算肿瘤体积,连续用药14 d后处死小鼠,剥离皮下肿瘤称重并计算抑瘤率。采用Western印迹、免疫组化方法检测Mac2-BP、VEGF的表达。结果与NS组相比,TMP组、DDP组、TMP+DDP组的瘤体增长均减慢,TMP+DDP组瘤体增长减慢最明显。TMP组、DDP组、TMP+DDP组抑瘤率分别为25.57%、45.24%和66.5%。采用金氏公式评价TMP+DDP对小鼠Lewis肺癌的抑制作用,TMP+DDP组0.85<q<1.15,表明TMP+DDP对小鼠Lewis肺癌有相加抑制作用。NS组中,VEGF与Mac2-BP表达成正相关(Western印迹法r=0.713,P=0.021,免疫组化法r=0.653,P=0.041)。与NS组相比,Mac2-BP、VEGF在TMP组、DDP组、TMP+DDP组表达明显降低(P<0.05),TMP+DDP组表达最低(P<0.05)。两种检测方法结果一致。结论 TMP+DDP对小鼠Lewis肺癌有相加抑制作用,能抑制肿瘤血管生成,其机制可能与抑制Mac2-BP、VEGF表达有关。 [ Abstract] Objective To investigate the effect of tetramethylpyrazine (TMP) combined with cisplatin (DDP) on the expression of Mac2-binding protein(Mac2-BP) and vascular endothelial growth factor(VEGF) in mice with lung cancer. Methods C57BL/6 mice were subcutaneously inoculated with Lewis lung adenocarcinoma cells, and Lewis lung adenocareinoma mouse xenograft model was established. Forty mice were randomly divided into four groups: normal saline group(NS group ,0. 9% NaC1,0. 2 ml), TMP group (TMP 100 mg/kg,O. 2 ml), DDP group (DDP 2 mg/kg,0.2 ml), TMP plus DDP group (doses as above ,0.2 ml totally) with 10 mice in each group. After 2 drug intervention, following 14 days of inoculation, the tumor diameter was measured every two days to calculate the tumor volume. The mice were sacrificed after 14 days of continuous medication, and the subcutaneous tumors were weighed after stripping to calculate the inhibitory rate. The expressions of Mac2-BP and VEGF was detected by Western blot and immunhistochemistry. Results Compared with NS group, the tumor growth rate of TMP group, DDP group and TMP + DDP group was slowed down, and the tumor growth rate in the TMP + DDP group was decreased most significantly. The inhibitory rate of TMP group, DDP group and TMP + DDP group was 25.57% , 45.24% and 66.5% ,respectively. Kim's formula was used to evaluate the synergy of the combined treatment. The q values for TMP + DDP group was 0.85 〈 q 〈 1. 15, suggesting the additive inhibition of combined TMP and DDP in mice Lewis lung cancer. A positive correlation was observed between Mac2-BP and VEGF expressions of NS group ( Western blotting r = 0. 713, P = 0. 021, immunohistochemistry r = 0. 653, P = 0. 041 ). Compared with NS group, the expression of Mac2-BP and VEGF in the TMP group, DDP group, TMP + DDP group was dramatically decreased ( P 〈 0.05 ) , and that in TMP + DDP group was significantly lower than in TMP and DDP groups (P 〈 O. 05 ). The results deduced by immunhistochemistry and Western blot were consistent. Conclusion Combination of TMP and cisplatin has additive anti-tumor effect on lung cancer bearing C57BL/6 mice. It can inhibit tumor angiogenesis and the mechanism may be related to the inhibition of Mac2-BP and VEGF expression. TMP can inhibit the growth of implanted Lewis lung carcinoma xenografted by inhibiting the expression of Mac2-BP and VEGF and the angiogenesis. TMP combined with DDP can improve the effect of chemotherapy and enhance the inhibiting effect of angiogenesis. Mac2-BP may promote the angiogenesis of lung cancer by up-regulating the expression of VEGF.
出处 《军事医学》 CAS CSCD 北大核心 2015年第10期751-754,764,共5页 Military Medical Sciences
关键词 川芎嗪 肺癌 血管生成 血管内皮生长因子 Mac2-BP/90K/LGALS3BP tetramethylpyrazine lung cancer angiogenesis VEGF Mac2-BP/90K/LGALS3 BP
  • 相关文献

参考文献15

  • 1Benazzi C, A1-Dissi A, Chau CH, et al. Angiogcncsis in sponta neous tumors and implications tor comparative tumor biology[ J ]. Sci World J, 2014,2014:919570.
  • 2Piccolo E, Tinari N, Semeraro D, et al. LGALS3BP, Lectin ga- lactoside-binding soluble 3 binding protein, induces vascular en- dothelial growth factor in human breast cancer cells and promotes angiogenesis[ J]. J Mol Med, 2013, 91 ( 1 ) : 83 - 94.
  • 3李雷宇,张俊华,张银旭,李伟.川芎嗪抗大肠癌sw620裸鼠移植瘤血管生成及抑瘤机制的实验研究[J].东南大学学报(医学版),2010,29(5):519-523. 被引量:10
  • 4郭久宏,彭胜国,康玉斌.川芎嗪对小鼠Lewis细胞增殖与凋亡的影响[J].新乡医学院学报,2014,31(1):26-28. 被引量:2
  • 5刘志良,崔伦伯.川芎嗪对小鼠小细胞肺癌血管生长和VEGF表达的抑制[J].辽宁医学院学报,2009,30(1):13-16. 被引量:11
  • 6丁大连,亓卫东,张梅,王苹,蒋海燕,Richard Salvi.顺铂及其耳毒性[J].中华耳科学杂志,2008,6(2):125-133. 被引量:45
  • 7Martinez VG, Moestrup SK, Holmskov U, et al. The conserved scavenger receptor cysteine-rich supeffamily in therapy and diag- nosis[J]. Pharmacol Rev, 2011,63(4): 967-1000.
  • 8Tinari N, Lattanzio R, Querzoli P, et al. High expression of Mac2-BP (Mac-2 BP) is associated with poor survival in node- negative breast cancer patients not receiving adjuvant systemic therapies[J], lnt J Cancer, 2009, 124(2) : 333 -338.
  • 9Fornarini B, D'Ambrosio C, Natoli C, et al. Adhesion to Mac2- BP ( Mae-2 BP) as a mechanism for lymphoma drug resistance in vivo[J]. Blood, 2000, 96(9) : 3282 -3285.
  • 10Ozaki Y, Kontani K, Hanaoka J, et al. Expression and immuno- genicity of a tumor-associated antigen, Mae2-BP/Mac-2 binding protein, in lung carcinoma[ J1. Cancer, 2002, 95(9) : 1954 -1962.

二级参考文献44

  • 1刘锦蓉,叶松柏.川芎嗪抗肿瘤转移作用及其机理[J].中国药理学与毒理学杂志,1993,7(2):149-152. 被引量:68
  • 2王文武,戴西湖,欧阳学农.川芎嗪对小鼠Lewis肺癌的治疗作用[J].中国临床药理学与治疗学,2005,10(4):421-423. 被引量:10
  • 3梁爱群.川芎嗪的药理及机理研究[J].时珍国医国药,2005,16(6):532-533. 被引量:85
  • 4[1]Rosenherg B,VanCamp L,Trosko VH,et al.Platinum compounds:a new class of potent antitumour agents.Nature,1969,222 (5191):p.385-386.
  • 5[2]Nitiss JL.A copper connection to the uptake of platinum anticancer drags.Proc Natl Acad Sci USA,2002,99(22):13963-13965.
  • 6[3]Ohashi K,Kajiya K,Inaba S,et al.Copper(Ⅱ) protects yeast against the toxicity of cisplatin inde pendently of the induction of metallothionein and the inhibition of platinum uptake.Biochem Biophys Res Commnn,2003,310(1):148-152.
  • 7[4]Katano K,Safaei R,Samimi G,et al.Confocal microscopic analysis of the interaction between cisplatin and the copper transporter ATP7B in human ovarian carcinoma cells.Clin Cancer Res,2004,10(13):p.4578-4588.
  • 8[6]Ding D,Jiang H,Salvi R.Cisplatin uptake into mammalian cochlear hair cells in vitro.Abstr Assoc Res Otolaryngol,2007.
  • 9[7]Marklund L,Andersson B,Behnam-Motlagh P,et al.Cellular potassium ion deprivation enhances apoptosis induced by cisplatin.Basic Clin Pharmacol Toxicol,2004,94(5):p.245-251.
  • 10[8]Hamers FP,Wijbenga J,Wolters FL,et al.Cisplatin ototoxicity involves organ of Corti,stria vascularis and spiral ganglion:modulation by alphaMSH and ORG 2766.Audiol Neurootol,2003,8(6):305-315.

共引文献62

同被引文献112

  • 1张永江,陈洪岩,夏长友.实验研究中实验动物的选择及其相关干扰因素[J].中国实验动物学杂志,2002,12(5):316-319. 被引量:9
  • 2黄继汉,黄晓晖,陈志扬,郑青山,孙瑞元.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):1069-1072. 被引量:1337
  • 3钟大放.以加权最小二乘法建立生物分析标准曲线的若干问题[J].药物分析杂志,1996,16(5):343-346. 被引量:581
  • 4Ferlay J,Soerjomataram I,Dikshit R,et al. Cancer incidenceand mortality worldwide :sources, methods and major pat- terns in GLOBOCAN 2012 [J]. Int J Cancer, 2015,136 (5) : 359-386.
  • 5Gitton Y,Dahmane N,Baid S,et al. A gene expression map of human chromosome 21 orthologues in the mouse [J]. Nature, 2002,420(6915 ) : 586-590.
  • 6Dragani TA. 10 years of mouse cancer modifierloci:human- relevance [J]. Cancer Res, 2003,63 (12) : 3011-3018.
  • 7Jackson EL,Willis N, Mercer K,et al. Analysis of lung tumor initiation and progression using conditional ex- pression of oncogenic K-ras [J]. Genes Dev,2001,15(24): 3243-3248.
  • 8Ohashi K,Rai K,Fujiwara Y,et al. Induction of lung ade- nocarcinoma in transgenic mice expressing activated EGFR driven by the SP-C promoter [J]. Cancer Sci,2008,99(9) : 1747-1753.
  • 9Gerald R, Cunha N, Laurence B. Use of sub-renal cap- sule transplantation in developmental biology [J]. Differ- entiation, 2015,10(7) : 1-7.
  • 10Iochmann S,Lerondel S,Bl~chet C,et al. Monitoring of tumour progression using bioluminescence imaging and computed tomography scanning in a nude mouse ortho- topic model of human small cell lung cancer [J]. Lung Cancer, 2012,77 ( 1 ) : 70-76.

引证文献7

二级引证文献26

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部