血管生成抑制剂血管抑素对CC531结肠癌细胞体外生长及腹腔镜腹膜癌病动物模型的影响。

Effects of the angiogenesis inhibitor angiostatin on the growth of CC531 colon carcinoma cells in vitro and in a laparoscopic animal model of peritoneal carcinomatosis.

作者信息

Nestler G, Schulz H U, Tautenhahn J, Kuhn R, Krüger S, Lippert H, Pross M

机构信息

Department of Surgery, Faculty of Medicine, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.

出版信息

Int J Colorectal Dis. 2006 May;21(4):314-20. doi: 10.1007/s00384-005-0040-2. Epub 2005 Oct 5.

DOI:10.1007/s00384-005-0040-2

PMID:16205930

Abstract

BACKGROUND

As angiogenesis is one of the key steps in tumor growth, invasion, and metastasis, antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. We investigated the cytotoxic, anti-adhesive, and anti-invasive effects of angiostatin in vitro and on intraperitoneal tumor growth in a laparoscopic rat model of peritoneal carcinomatosis using CC531 colon adenocarcinoma cells.

METHODS

The in vitro adhesion and cytotoxicity assays were performed with microtiter plates, and the invasion assay with Transwell dual chambers. Normal saline was used as control. In in vivo experiments, CC531 adenocarcinoma cells were intraperitoneally given to Wistar Albino Glaxo rats after the establishment of a pneumoperitoneum. The animals received angiostatin in different doses intraperitoneally, and in some, angiostatin was additionally administered subcutaneously. Saline was used as control. After 21 days, the animals were euthanized to determine the intra-abdominal tumor weight.

RESULTS

In in vitro experiments, there was no effect of angiostatin on the viability of tumor cells in the cytotoxicity assay, but there was a significant inhibition of tumor cell adhesion and invasion (p<0.05 and p<0.01) in all angiostatin concentrations. In in vivo experiments, an intraperitoneal application of 20 microg angiostatin, but not 10 microg, significantly (p<0.005) decreased the intraperitoneal tumor weight compared with controls. This effect was most pronounced after the combined intraperitoneal and subcutaneous applications.

CONCLUSION

Angiostatin given intraperitoneally at a dose of 20 microg alone or in combination with subcutaneous application significantly diminishes intraperitoneal tumor growth in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic surgery for colorectal cancer.

摘要

背景

由于血管生成是肿瘤生长、侵袭和转移的关键步骤之一，抗血管生成疗法被认为是一种有吸引力的抗肿瘤治疗方法。我们使用CC531结肠腺癌细胞，在腹腔镜大鼠腹膜癌模型中研究了血管抑素的细胞毒性、抗黏附及抗侵袭作用，以及其对腹腔内肿瘤生长的影响。

方法

采用微量滴定板进行体外黏附及细胞毒性试验，使用Transwell双室进行侵袭试验。以生理盐水作为对照。在体内实验中，对建立气腹后的Wistar白化Glaxo大鼠腹腔注射CC531腺癌细胞。动物腹腔注射不同剂量的血管抑素，部分动物还额外皮下注射血管抑素。以生理盐水作为对照。21天后，对动物实施安乐死以测定腹腔内肿瘤重量。

结果

在体外实验中，血管抑素在细胞毒性试验中对肿瘤细胞活力无影响，但在所有血管抑素浓度下均显著抑制肿瘤细胞黏附及侵袭（p<0.05和p<0.01）。在体内实验中，与对照组相比，腹腔注射20μg血管抑素可显著（p<0.005）降低腹腔内肿瘤重量，但10μg剂量则无此作用。这种作用在腹腔内和皮下联合应用后最为明显。