Insulin-like growth factor-binding protein 3 inhibits growth of experimental colocarcinoma
Insulin-like growth factor-binding protein 3 inhibits growth of experimental colocarcinoma
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DOI：
10.1016/j.surg.2004.04.020
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发表时间：
2004-08-01
期刊：
影响因子：
3.8
通讯作者：
Whelan, RL
中科院分区：
文献类型：
--
作者：
Kirman, I;Poltoratskaia, N;Whelan, RL
背景我们以前已经证明，一个重要的细胞生长调节蛋白，胰岛素样生长因子结合蛋白3（IGFBP-3）是开放式手术后，但不是腹腔镜手术后，在外周血中耗尽。我们还证明了IGTBP-3在体外诱导人结肠癌细胞凋亡。我们在此报道IGFBP-3对结肠上皮细胞在体内生长的影响。使用两种肿瘤模型：用氧化偶氮甲烷（AOM）化学诱导的致癌作用和接种同系结肠癌细胞。在AOM诱导的癌变中，野生型（WT）和IGFBP-3转基因（IGFBP-3-TG）CD 1小鼠注射AOM，并研究结肠中异常隐窝病灶（ACF）的数量。在同系模型中，BALB/c小鼠接种CT 26细胞。对照组给予生理盐水，而试验组每周给予IGFBP-3。在建立后2.5周评估肿瘤重量。IGFBP-3转基因小鼠的异常隐窝病灶数（1.3 ± 1.1）显著低于WT对照组（6.8 ± 6.0）（P <0.05）。001）。此外，接受IGFBP-3的BALB/c小鼠中的CT 26肿瘤（0.364 +/- 0.165 g）比WT对照（0.742 +/- 0.261 g）显著更小（P <0.01）。IGFBP-3在实验模型中抑制结肠肿瘤的发展，并可能有望作为肿瘤患者的辅助治疗。
Background. We have previously shown that an important cell growth regulatory protein, insulin-like growth factor-binding protein 3 (IGFBP-3) is depleted in peripheral blood after open-but not laparoscopic-surgery. We have also demonstrated that IGTBP-3 induces apoptosis of human colon cancer cells in vitro. We report here the effect of IGFBP-3 on the growth of colonic epithelial cells in vivo.Methods. Two tumor models were used: chemically induced carcinogenesis with azoxymethane (AOM) and inoculation of syngeneic colon cancer cells. In AOM-induced carcinogenesis, wild type (WT) and IGFBP-3 transgenic (IGFBP-3-TG) CD1 mice were injected with AOM and the number of aberrant crypt foci (ACF) in the colon studied. In the syngeneic model, BALB/c mice were inoculated with CT26 cells. The control group received saline, while the test group was administered IGFBP-3 weekly. Tumor weight was assessed 2.5 weeks after establishment.Results. The number of aberrant crypt foci was significantly lower in IGFBP-3 transgenic mice (1.3 +/- 1.1) compared to WT controls (6.8 +/- 6 0) (P < . 001). Further, CT26 tumors were significantly smaller in BALB/c mice that received IGFBP-3 (0.364 +/- 0.165 g) than in WT controls (0.742 +/- 0.261 g) (P < .01).Conclusions. IGFBP-3 inhibits the development of colonic tumors in experimental models and may hold promise as an adjuvant therapy for Patients with neoplasms.