您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2015, Vol. 53 ›› Issue (9): 8-12.doi: 10.6040/j.issn.1671-7554.0.2015.219

• 基础医学 • 上一篇    下一篇

小鼠胚胎干细胞分泌因子对前列腺癌细胞作用的体外研究

翟红运1, 张登禄1, 王光杰1, 孔峰2, 程广辉2, 赵升田1   

  1. 1. 山东大学第二医院 泌尿外科, 山东 济南 250033;
    2. 山东大学第二医院 中心实验室, 山东 济南 250033
  • 收稿日期:2015-02-28 出版日期:2015-09-10 发布日期:2015-09-10
  • 通讯作者: 赵升田。E-mail:zhaoshengtian@sdu.edu.cn E-mail:zhaoshengtian@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81272815);泰山学者特聘教授科研基金

Effects of factors secreted by mouse embryonic stem cells on prostate cancer cells in vitro

ZHAI Hongyun1, ZHANG Denglu1, WANG Guangjie1, KONG Feng2, CHENG Guanghui2, ZHAO Shengtian1   

  1. 1. Department of Urology, Jinan 250033, Shandong, China;
    2. Central Laboratory, Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Received:2015-02-28 Online:2015-09-10 Published:2015-09-10
  • Contact: 赵升田。E-mail:zhaoshengtian@sdu.edu.cn E-mail:zhaoshengtian@sdu.edu.cn

摘要: 目的 研究小鼠胚胎干细胞(ESC)分泌因子对前列腺癌细胞RM-1生物学特性的影响,并探讨其作用机制。方法 采用Transwell小室在体外建立ESC联合小鼠胚胎成纤维细胞(MEF)与RM-1细胞的非接触式共培养体系作为实验干预(实验组),同时建立MEF与RM-1细胞的共培养体系作为阴性对照(对照组)。共培养72 h后,检测实验组与对照组RM-1细胞的增殖水平,比较两组细胞的形态学、细胞周期、凋亡水平、迁移与侵袭能力的差异。结果 与对照组比较,实验组RM-1细胞的形态表现为排布稀疏,分裂减少,死亡增多,部分细胞呈现凋亡迹象;实验组RM-1细胞增殖减慢(P<0.01),细胞周期存在G1→S期阻滞且凋亡增加,以晚期凋亡为主(P均<0.01);实验组RM-1细胞的迁移和侵袭能力减弱(P均<0.05)。结论 ESC分泌因子可通过阻滞RM-1细胞周期、促进其凋亡使RM-1细胞的增殖减慢,同时减弱其迁移与侵袭能力而发挥抗肿瘤作用。

关键词: 胚胎干细胞, 分泌因子, 前列腺癌细胞RM-1, 肿瘤, 细胞环境, 小鼠

Abstract: Objective To study the effects of factors secreted by mouse embryonic stem cells (ESC) on the biological characteristics of prostate cancer cells RM-1 and to explore the mechanism. Methods A non-contact co-culture system was established with Transwell chambers in vitro. The chambers connecting ESC combined with mouse embryonic fibroblasts (MEF) and RM-1 cells served as experimental group, while the chambers connecting MEF and RM-1 cells were negative controls. After cells were co-cultured for 72 h, the proliferation of RM-1 cells in the two groups were measured. Differences of RM-1 cells in cell morphology, cell cycle, apoptotic level, migration and invasion ability between the two groups were observed. Results The RM-1 cells in experimental group were loosely arranged with less cell division and more cell death, and some cells showed signs of apoptosis. The RM-1 cells in experimental group proliferated more slowly (P<0.01), with cell cycle arrest between phase G1 and S in addition with increased apoptosis, especially late stage apoptosis (both P<0.01). The RM-1 cells in experimental group showed weaker migration and invasion ability (both P<0.05). Conclusion The factors secreted by ESC exhibited anti-tumor effects. They inhibited RM-1 cell proliferation by arresting cell cycle, increasing cell apoptosis, and weakening cell migration and invasion ability.

Key words: Secreted factors, Prostate cancer cell RM-1, Cellular environment, Embryonic stem cell, Mouse, Neoplasia

中图分类号: 

  • R737.25
[1] Abbott DE, Postovit LM, Seftor EA, et al. Exploiting the convergence of embryonic and tumorigenic signaling pathways to develop new therapeutic targets[J]. Stem Cell Rev, 2007, 3(1): 68-78.
[2] Costa FF, Seftor EA, Bischof JM, et al. Epigenetically reprogramming metastatic tumor cells with an embryonic microenvironment[J]. Epigenomics, 2009, 1(2): 387-398.
[3] Bissell MJ, Hines WC. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression[J]. Nat Med, 2011, 17(3): 320-329.
[4] Joel M, Sandberg CJ, Boulland JL, et al. Inhibition of tumor formation and redirected differentiation of glioblastoma cells in a xenotypic embryonic environment[J]. Dev Dyn, 2013, 242(9): 1078-1093.
[5] Postovit LM, Margaryan NV, Seftor EA, et al. Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells[J]. Proc Natl Acad Sci U S A, 2008, 105(11): 4329-4334.
[6] Palumbo A Jr, Ferreira LB, Reis de Souza PA, et al. Extracellular matrix secreted by reactive stroma is a main inducer of pro-tumorigenic features on LNCaP prostate cancer cells[J]. Cancer Lett, 2012, 321(1): 55-64.
[7] Tandon N, Marolt D, Cimetta E, et al. Bioreactor engineering of stem cell environments[J]. Biotechnol Adv, 2013, 31(7): 1020-1031.
[8] Cetnar JP, Beer TM. Personalizing prostate cancer therapy: the way forward[J]. Drug Discov Today, 2014, 19(9): 1483-1487.
[9] Jozefczuk J, Drews K, Adjaye J. Preparation of mouse embryonic fibroblast cells suitable for culturing human embryonic and induced pluripotent stem cells[J]. J Vis Exp, 2012, 64, pii: 3854. doi: 10.3791/3854.
[10] Catalano V, Turdo A, Di Franco S, et al. Tumor and its microenvironment: a synergistic interplay[J]. Semin Cancer Biol, 2013, 23(6 Pt B): 522-532.
[11] Liu W, Vivian CJ, Brinker AE, et al. Microenvironmental influences on metastasis suppressor expression and function during a metastatic cell's journey[J]. Cancer Microenviron, 2014, 7(3): 117-131.
[12] Zhang X, Nie D, Chakrabarty S. Growth factors in tumor microenvironment[J]. Front Biosci, 2010, 15: 151-165.
[13] Hanna E, Quick J, Libutti SK. The tumor microenvironment: a novel target for cancer therapy[J]. Oral Dis, 2009, 15(1): 8-17.
[14] 詹秀琴, 姜泽群. 干细胞共培养技术在医学研究中的应用[J]. 中国细胞生物学学报, 2014, 36(8): 1178-1185. ZHAN Xiuqin, JIANG Zequn. Cell co-culture technique in the medical research of stem cells[J]. Chinese Journal of Cell Biology, 2014, 36(8): 1178-1185.
[15] Lu X, Park SH, Thompson TC, et al. Ras-induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation[J]. Cell, 1992, 70(1): 153-161.
[16] 童锦禄, 冉志华. G1/S检测点调控机制研究进展[J]. 世界华人消化杂志, 2005, 13(16): 2036-2039.
[17] Ouyang L, Shi Z, Zhao S, et al. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis[J]. Cell Prolif, 2012, 45(6): 487-498.
[18] Jäger R, Zwacka RM. The enigmatic roles of caspases in tumor development[J]. Cancers (Basel), 2010, 2(4): 1952-1979.
[19] Yilmaz M, Christofori G. Mechanisms of motility in metastasizing cells[J]. Mol Cancer Res, 2010, 8(5): 629-642. [20] Stetler-Stevenson WG, Gavil NV. Normalization of the tumor microenvironment: evidence for tissue inhibitor of metalloproteinase-2 as a cancer therapeutic[J]. Connect Tissue Res, 2014, 55(1): 13-19.
[21] Hendrix MJ, Seftor EA, Seftor R, et al. Reprogramming metastatic tumour cells with embryonic microenvironments[J]. Nat Rev Cancer, 2007, 7(4): 246-255.
[22] Giuffrida D, Rogers IM, Nagy A, et al. Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth[J]. Cell Prolif, 2009, 42(6): 788-798.
[23] Buzhor E, Leshansky L, Blumenthal J, et al. Cell-based therapy approaches: the hope for incurable diseases[J]. Regen Med, 2014, 9(5): 649-672.
[24] Schulman IH, Suncion V, Karantalis V, et al. Clinical research skills development program in cell-based regenerative medicine[J]. Stem Cells Transl Med, 2015, 4(2): 118-122.
[1] 杨晓倩 季静 刘娜 郭冬梅 崔癉. 三氯化铁及络合铁的抗银屑病作用研究[J]. 山东大学学报(医学版), 2209, 47(6): 114-117.
[2] 王伟 王沂峰 张岭梅 林琼燕 黄菊. 人卵巢癌OVCAR3细胞系中侧群细胞的分离及其成瘤性、侵袭性的实验研究[J]. 山东大学学报(医学版), 2209, 47(6): 8-11.
[3] 张士宝 刘庆勇 阮喜云 陈杰 张建军 李宗武 杨广笑 王全颖. NT4-SAC-HA2-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[4] 李波波 李道堂 刘曙光 王兴武. 食管癌患者血清中DKK-1的表达[J]. 山东大学学报(医学版), 2209, 47(6): 58-61.
[5] 鹿向东 杨伟 徐广明 曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[6] 黄方 康瑞 吴春林. VEGFC、NF-κBp65及Survivin在鼻咽癌中的表达及临床意义[J]. 山东大学学报(医学版), 2209, 47(6): 83-.
[7] 段淑红 刘凯 尹海燕 赵世斗 刘丰韬. 凝集素受体WGA、RCA和ECL在过量维甲酸致昆明小鼠腭裂发生中的作用[J]. 山东大学学报(医学版), 2209, 47(6): 47-.
[8] 白洁,刘玥,张宁宁,温洋,彭芸,程华. 中枢神经肿瘤样脱髓鞘病2例[J]. 山东大学学报 (医学版), 2020, 1(9): 103-105.
[9] 王稳,董绍华,田翔宇,崔秀娟. 盆腹腔多发脾种植误诊为妇科肿瘤1例[J]. 山东大学学报 (医学版), 2020, 1(9): 116-118.
[10] 王剑,周文婧,薛知易,刘晓菲. 脑胶质母细胞瘤模型研究概况及类脑模型的研发应用[J]. 山东大学学报 (医学版), 2020, 1(8): 74-80.
[11] 刘琚,吴强,于璐跃,林枫茗. 基于深度学习的脑肿瘤图像分割[J]. 山东大学学报 (医学版), 2020, 1(8): 42-49, 73.
[12] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1-6.
[13] 龙婷婷,谢明,周璐,朱俊德. Noggin蛋白对小鼠脑缺血再灌注损伤后学习和记忆能力与齿状回结构的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 15-23.
[14] 路璐,孙志钢,张楠. 继发性嗜血细胞综合征1例[J]. 山东大学学报 (医学版), 2020, 1(7): 122-124.
[15] 董伟,邢乃栋,吕家驹,刘帅,孙亮,曹庆伟,董宇昊,刘钊,丁森泰. 靶向抑制有丝分裂驱动蛋白治疗多西紫杉醇耐药前列腺癌的体外疗效[J]. 山东大学学报(医学版), 2017, 55(9): 23-30.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!