MUC1-GEM-PBCA-NP、CA199-GEM-PBCA-NP静注对裸鼠胰腺癌种植瘤的抑制作用对比观察Comparison of anti-tumor effects between MUC1-GEM-PBCA-NP and CA199-GEM-PBCA-NP on pancreatic cancer xenografts in nude mice
张林;侯艳红;李春梅;刘浩润;
摘要(Abstract):
目的比较黏性蛋白1(MUC1)与糖类抗原199(CA199)单克隆抗体偶联吉西他滨聚氰基丙烯酸正丁酯纳米粒(MUC1-GEM-PBCA-NP、CA199-GEM-PBCA-NP)对裸鼠胰腺癌种植瘤的抑制作用。方法采用皮下种植法建立胰腺癌种植瘤荷瘤动物模型,将制模成功的裸鼠随机分为6组各7只;A组静注2.5 mg/kg的MUC1-GEM-PBCA-NP,B组静注等量CA199-GEM-PBCA-NP,C组静注等量吉西他滨聚氰基丙烯酸正丁酯纳米粒(GEM-PBCA-NP),D组静注等量吉西他滨,E组静注等量聚氰基丙烯酸正丁酯纳米粒(PBCA-NP),F组静注等量生理盐水,各组均经尾静脉注射,每5 d重复治疗1次。35 d后比较各组移植瘤肿瘤体积、抑瘤率。另取9只荷瘤裸鼠并分为3组各3只,a组静注10 mg/kg MUC1-Cy3-PBCA-NP,b组静注10 mg/kg CA199-Cy3-PBCA-NP,c组静注等量Cy3-PBCA-NP,比较各组Cy3荧光信号强度。结果与其余各组比较,A组肿瘤体积小,抑瘤率高(P均<0.05);与C、D组比较,B组肿瘤体积小,抑瘤率高(P均<0.05);与F组比较,C、D组肿瘤体积小,抑瘤率高(P均<0.05)。a组荧光信号强度显著强于其余两组,主要定为于细胞胞膜及胞质中;b组荧光信号强度弱于a组,且主要定为于细胞胞膜,胞质中荧光信号较弱;c组荧光信号微弱,仅部分细胞胞膜可见。结论 MUC1-GEM-PBCA-NP、CA199-GEM-PBCA-NP均可抑制裸鼠胰腺癌种植瘤,但抗MUC1作为载药纳米粒的修饰分子时抑瘤效果更佳。
关键词(KeyWords): 胰腺癌;黏性蛋白1;糖类抗原199;吉西他滨聚氰基丙烯酸正丁酯纳米粒
基金项目(Foundation):
作者(Author): 张林;侯艳红;李春梅;刘浩润;
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DOI:
参考文献(References):
- [1] 中国抗癌协会胰腺癌专业委员会.胰腺癌综合诊治指南(2018版)[J].中华外科杂志,2018,56(7):481-493.
- [2] 李春梅,张林,侯艳红,等.聚氰基丙烯酸正丁酯荧光纳米微球的制备及其在裸鼠体内分布情况研究[J].胃肠病学和肝病学杂志,2015,24(12):1464-1467.
- [3] 李春梅,张林,侯艳红,等.抗EGFR单抗偶联吉西他滨聚氰基丙烯酸正丁酯纳米粒对胰腺癌的靶向治疗[J].世界华人消化杂志,2015,23(12):1890-1896.
- [4] AMR I,MAZEN S,AMER H,et al.Serum CA199 response to neoadjuvant therapy is predictive of tumor size decrease and survival in pancreatic adenocar- cinoma[J].J Am Coll Surg,2018,227(4S1):248-249.
- [5] TSANG E S,WONG H L,WANG Y,et al.Outcomes and characteristics of patients receiving second-line therapy for advanced pancreatic cancer[J].Am J Clin Oncol,2019,42(2):196-200.
- [6] BOJIC-TRBOJEVIC Z,KRIVOKUACM J,VRZIC-PETRONIJEVIC S,et al.Expression of tumor associated antigens CA 15-3 and CA 19-9 in trophoblast of the normal human placenta[J].Eur J Gynaecol Oncol,2012,33(3):281-284.
- [7] 袁耀宗,何相宜.胰腺癌临床研究的热点问题[J].中华消化杂志,2011,31(5):356-357.
- [8] 尼露排.阿布都热黑依木,张弘纲.晚期胰腺癌的内科治疗现状[J].癌症进展,2017,15(4):371-376.
- [9] OKUSAKA T,FURUSE J.Recent advances in chemotherapy for pancreatic cancer:evidence from Japan and recommendations in guidelines[J].J Gastroenterol,2020,55(4):369-382.
- [10] PECORELLI N,PAGNANELLI M,CINELLI L,et al.Postoperative outcomes and functional recovery after preoperative combination chemotherapy for pancreatic cancer:a propensity score-matched study[J].Front Oncol,2019,6(9):1299.
- [11] SPRINGFELD C,JAGER D,BüCHLERU M W,et al.Chemotherapy for pancreatic cancer[J].Presse Med,2019,48(3 Pt 2):e159-e174.
- [12] HENKEL E,HERNANDEZ B,MICHALEK J E,et al.Combination chemotherapy for pancreatic cancer in older adults:Efficacy and safety analysis of patients at a majority-Hispanic NCI-designated cancer center[J].J Clin Oncol,2019,37(4Suppl):389-389.
- [13] GAO W,HAN Y.Advances in molecular targeted therapy of pancreatic cancer[J].Tumor,2018,38(2):157-163.
- [14] GAO N,BOZEMAN E,QIAN W P,et al.Abstract 4593:Targeted therapy of pancreatic cancer by intraperitoneal delivery of uPAR-targeted theranostic nanoparticles[J].Cancer Research,2014,74(19 Suppl):4593-4593.
- [15] TANAKA S.Molecular pathogenesis and targeted therapy of pancreatic cancer[J].Ann Surg Oncol,2016,23(Suppl2):197-205.
- [16] 李春梅,张林,李楠.纳米粒子靶向治疗胰腺癌的研究进展[J].胃肠病学和肝病学杂志,2015,24(4):389-393.
- [17] 张重捷,邹奇,陈杰,等.MUCl黏蛋白1抗体标记超顺磁纳米粒在胰腺癌裸鼠模型中的实验研究[J].中国医学影像学杂志,2017,25(10):721-725.
- [18] GIRGIS M D,FEDERMAN N,ROCHEFORT M M,et al.An engineered anti-CA19-9 cys-diabody for positron emission tomography imaging of pancreatic cancer and targeting of polymerized liposomal nanoparticles[J].J Surg Res,2013,185(1):45-55.