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苏拉明对人食管癌细胞的体内外作用

Effect of suramin on human esophageal cancer cells in vitro and in vivo.

作者信息

Shin R, Naomoto Y, Kamikawa Y, Tanaka N, Orita K

机构信息

First Dept. of Surgery, Okayama University Medical School, Japan.

出版信息

Scand J Gastroenterol. 1997 Aug;32(8):824-8. doi: 10.3109/00365529708996541.

Abstract

BACKGROUND

Suramin disrupts several kinds of growth factor receptors. Since human esophageal squamous cell carcinoma expresses abundant epidermal growth factor receptors (EGFR) and proliferates in an autocrine and paracrine manner, it was expected that suramin inhibits tumor growth by disrupting EGFR.

METHODS

We studied the effect of suramin on the human esophageal squamous cell carcinoma cell line KEsC-II in vitro and in an animal model.

RESULTS

Cell proliferation was stimulated at a low concentration and inhibited at a high concentration of suramin in vitro. Since autophosphorylation of EGFR was stronger at the low concentration and weaker at the high concentration of suramin compared with the control, the effect of suramin was thought to be via phosphorylation of receptors. In the animal model tumor growth was significantly stimulated in the suramin-treated group compared with the control group, and the BrdU labeling index was also higher in the suramin-treated group.

CONCLUSIONS

As it was impossible to increase the dose of suramin intravenously because of side effects, administration of suramin by another method, such as subcutaneous injection around the tumor, may increase the concentration of suramin in the tumor tissue and promote the anti-tumor effect of suramin.

摘要

背景

苏拉明可破坏多种生长因子受体。鉴于人食管鳞状细胞癌表达丰富的表皮生长因子受体(EGFR),并以自分泌和旁分泌方式增殖,因此推测苏拉明可通过破坏EGFR来抑制肿瘤生长。

方法

我们在体外和动物模型中研究了苏拉明对人食管鳞状细胞癌细胞系KEsC-II的作用。

结果

在体外,低浓度的苏拉明刺激细胞增殖,高浓度则抑制细胞增殖。与对照组相比,低浓度苏拉明时EGFR的自磷酸化更强,高浓度时则较弱,因此认为苏拉明的作用是通过受体磷酸化实现的。在动物模型中,与对照组相比,苏拉明治疗组的肿瘤生长明显受到刺激,且苏拉明治疗组的BrdU标记指数也更高。

结论

由于副作用,无法通过静脉内增加苏拉明的剂量,因此通过其他方法(如在肿瘤周围皮下注射)给予苏拉明可能会增加肿瘤组织中苏拉明的浓度,并增强苏拉明的抗肿瘤作用。

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