IGFBP-3对子宫内膜癌Ishikawa细胞增殖、凋亡及化疗敏感性的实验研究Effects of insulin-like growth factor binding protein-3(IGFBP-3) on proliferation,apoptosis and chemotherapeutic sensitivity of endometrial carcinoma Ishikawa cell
李艳辉;张晓燕;王泽华;汪宏波;
摘要(Abstract):
目的:探讨外源性胰岛素样生长因子结合蛋白-3(IGFBP-3)对Ishikawa细胞增殖、凋亡的影响及在抗肿瘤中其能否与顺铂起协同作用,并初步探讨IGFBP-3对垂体肿瘤转化基因1(PTTG1)表达的影响。方法:采用噻唑蓝(MTT)比色法检测IGFBP-3、顺铂对Ishikawa细胞的抑制率,计算半数抑制浓度;用流式细胞仪检测两药单用及合用对Ishikawa细胞周期、凋亡的影响;RT-PCR法检测药物干预后PTTG1表达量的变化。结果:(1)IGFBP-3对Ishikawa细胞增殖有明显抑制作用(IC50=1.00±0.12),且与顺铂有协同作用(CI<1);(2)IGFBP-3干预后Ishikawa细胞凋亡是对照的4.5倍(P<0.05);(3)顺铂、IGFBP-3均能下调PTTG1基因的表达,且以顺铂的下调作用明显。结论:在子宫内膜癌的Ishikawa细胞,观察到IGFBP-3具抗增殖、促凋亡的作用;IGFBP-3可能作为一种抗肿瘤剂用于临床。
关键词(KeyWords): 胰岛素样生长因子结合蛋白-3;顺铂;Ishikawa细胞;垂体肿瘤转化基因1;细胞凋亡;细胞周期
基金项目(Foundation):
作者(Authors): 李艳辉;张晓燕;王泽华;汪宏波;
DOI: 10.13283/j.cnki.xdfckjz.2008.05.017
参考文献(References):
- [1]Moschos SJ,Mantzoros CS.The role of the IGF system in cancer:from basic to clinical studies and clinical applica-tions[J].Oncology,2002,63:317-332
- [2]Kim HS,Ingermann AR,Tsubaki J,et al.Insulin-like growth factor-binding protein3induces caspase-dependent apoptosis through a death receptor-mediated pathway in MCF-7human breast cancer cells[J].Cancer Res,2004,64:2229-2237
- [3]Liu B,Lee KW,Anzo M,et al.Insulin-like growth factor-binding protein-3inhibition of prostate cancer growth in-volves suppression of angiogenesis[J].Oncogene,2007,26:1811-1819
- [4]Bradshaw C,Kakar SS.Pituitary tumor transforming gene:an important gene in normal cellular functions and tumori-genesis[J].Histol Histopathol,2007,22:219-226
- [5]王言奎,崔娜,李军,等.子宫内膜癌组织中垂体肿瘤转化基因PTTG的表达及其意义[J].中华妇产科杂志,2004,39:538-542
- [6]Liu B,Lee KW,Li H,et al.Combination therapy of insu-lin-like growth factor binding protein-3and retinoid X re-ceptor ligands synergize on prostate cancer cell apoptosis in vitro and in vivo[J].Clin Cancer Res,2005,11:4851-4856
- [7]Tsai SJ,Lin SJ,Cheng YM,et al.Expression and function-al analysis of pituitary tumor transforming growth factor-1in uterine leiomyomas[J].J Clin Endocrinol Metab,2005,90:3715-3723
- [8]Aoki Y,Watanabe M,Amikura T,et al.Adjuvant chemo-therapy as treatment of high-risk stageⅠandⅡendome-trial cancer[J].Gynecol Oncol,2004,94:333-339
- [9]Tfelt-Hansen J,Kanuparthi D,Chattopadhyay N.The e-merging role of pituitary tumor transforming gene in tu-morigenesis[J].Clin Med Res,2006,4:130-137
- [10]Chamaon K,Kirches E,Kanakis D,et al.Regulation of the pituitary tumor transforming gene by insulin-like-growth factor-I and insulin differs between malignant and non-neoplastic astrocytes[J].Biochem Biophys Res Commun,2005,331:86-92
- [11]Heaney AP,Fernando M,Melmed S.Functional role of estrogen in pituitary tumor pathogenesis[J].J Clin In-vest,2002,109:277-283
- [12]Zhou Y,Mehta KR,Choi AP,et al.DNA damage-induced inhibition of securin expression is mediated by p53[J].J Biol Chem,2003,278:462-470