中国组织工程研究

• 肿瘤干细胞 cancer stem cells • 上一篇    下一篇

顺铂在大鼠体内富集胃癌干细胞

李  荣1,李  蓉2,戴光荣3   

  1. 1陕西省西安市第五医院内三科,陕西省西安市  710082;2陕西省西安市第一医院消化内科,陕西省西安市710002;3陕西省延安市延安大学附属医学院消化内科,陕西省延安市  716000
  • 出版日期:2015-10-01 发布日期:2015-10-01
  • 通讯作者: 李荣,陕西省西安市第五医院内三科,陕西省西安市 710082
  • 作者简介:李荣,女,1969年生,湖南省长沙市人,汉族,1993年湖南医科大学毕业,硕士,副主任医师。
  • 基金资助:

    陕西省卫生厅科学研究基金(08H16)

Cisplatin therapy for in vivo enrichment of gastric cancer stem cells

Li Rong1, Li Rong2, Dai Guang-rong3   

  1. 1Third Department of Internal Medicine, Xi’an Fifth Hospital, Xi’an 710082, Shaanxi Province, China; 2Department of Gastroenterology, Xi’an No. 1 Hospital, Xi’an 710002, Shaanxi Province, China; 3Department of Gastroenterology, Affiliated Hospital of Yan’an University, Yan’an 716000, Shaanxi Province, China
  • Online:2015-10-01 Published:2015-10-01
  • Contact: Li Rong, Third Department of Internal Medicine, Xi’an Fifth Hospital, Xi’an 710082, Shaanxi Province, China
  • About author:Li Rong, Master, Associate chief physician, Third Department of Internal Medicine, Xi’an Fifth Hospital, Xi’an 710082, Shaanxi Province, China
  • Supported by:

    the Scientific Research Fund of Shaanxi Provincial Health Department, No. 08H16

摘要:

背景:肿瘤干细胞具有自我更新、耐药和转移成瘤能力,对肿瘤的发生、发展以及肿瘤的转移等具有重要的功能。目前,确认肿瘤干细胞的方法主要有2种,即体外瘤球培养实验以及小鼠体内成瘤实验,但临床上通过化疗在大鼠体内富集胃癌细胞尚缺乏研究报道。
目的:观察顺铂在大鼠体内富集胃癌干细胞的情况,研究其表面标志蛋白的筛选方法。
方法:建立BGC-823胃癌模型大鼠,采用随机对照方法将大鼠分为2组,实验组大鼠分别尾静脉注射质量浓度0.1,0.2,0.25,0.3 g/L的顺铂,而对照组则尾静脉注射生理盐水。经过3期化疗,最后得到富集胃癌干细胞组织;采用高通量蛋白芯片对肿瘤表面蛋白进行提取,并采用Western blot对芯片进行验证,比较顺铂在大鼠体内富集胃癌干细胞及其表面标志蛋白的筛选方法。
结果与结论:顺铂剂量为0.3 g/L×200 μL时治疗效果最佳,且化疗药物浓度越高,耐受力越差,不良反应发生率越高。移植瘤经苏木精-伊红染色验证均为癌组织;Western blot检测结果与蛋白芯片结果显示,HLA-DQ,PMP22和Claudin7蛋白在胃癌组织中表达增强,HLA-DR,CD14,CD16和CD56蛋白表达减弱。结果证实,顺铂化疗能够在体内富集胃癌干细胞,能够成功筛选出相应的表面标志物蛋白。

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 干细胞, 肿瘤干细胞, 顺铂, 富集胃癌干细胞, 表面标志蛋白, 筛选方法, 标志蛋白, 生长因子, 不良反应, 苏木精-伊红染色, Western blot, 胃癌模型

Abstract:

BACKGROUND: Tumor stem cells have self-renewal, drug resistance and metastasis tumorigenicity, which play an important role in occurrence, development and metastasis of tumors. Currently, there are two methods to identify tumor stem cells, namely, in vitro tumor sphere culture experiments and in vivo mouse tumorigenic experiments. However, there ia a lack of reports regarding clinically enriched gastric cancer cells by chemotherapy.
OBJECTIVE: To investigate the enrichment of rat gastric cancer stem cells by cisplatin, and to explore the screening methods for their surface marker proteins.
METHODS: BCG-823 gastric cancer model was established in rats, and then rat models were randomized into two groups: rats in experimental groups were subjected to intravenous injection of 0.1, 0.2, 0.25, 0.3 g/L cisplatin via the tail vein; those in control group were injected with normal saline via the tail vein. After three courses of chemotherapy, gastric stem cells-enriched tissues were collected. Tumor surface proteins were extracted using high-throughput protein microarray and identified by western blot assay. Effects of cisplatin on enrichment of rat gastric cancer stem cells and screening methods for surface marker proteins were compared.
RESULTS AND CONCLUSION: Cisplatin at a dose of 0.3 g/L×200 μL exhibited the best therapeutic effects, and moreover, with the dose increasing, the tolerance became worse and the incidence of adverse reaction became higher. Transplantation tumors were verified by hematoxylin-eosin staining. Western blot test results were similar to the findings of protein microarray method, that is, HLA-DQ, PMP22 and Claudin7 protein expressions increased in gastric tissues, but HLA-DR, CD14, CD16 and CD56 protein expression decreased. These findings suggest that cisplatin can be used to enrich gastric cancer stem cells in rats, and to successfully screen the corresponding surface marker proteins.

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

Key words: Stem Cells, Stomach Neoplasms, Tissue Engineering

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