Hotz Birgit, Buhr Heinz J, Hotz Hubert G
Department of Surgery I, Charité-Medical School, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
J Gastrointest Surg. 2008 May;12(5):900-6. doi: 10.1007/s11605-008-0507-x. Epub 2008 Mar 5.
We investigated the effect of suramin on tumor growth and spread in an immunocompetent, orthotopic rat model of pancreatic cancer and analyzed the tumor vasculature by intravital microscopy.
In vitro, rat ductal pancreatic cancer cells (DSL-6A) were incubated with suramin (10-800 microg/ml), and cell proliferation was assessed. In vivo, DSL-6A tumors were induced in the pancreas of Lewis rats. Animals received suramin (60 mg/kg, weekly i.p.) or the vehicle (controls). Treatment started after 3 days. Intravital microscopy after 1, 4, and 8 weeks quantified diameter, density, and permeability of tumor vessels. Primary tumor volume, local infiltration, and metastatic spread were determined at autopsy. Microvessel density was analyzed by immunohistochemistry.
In vitro, proliferation was inhibited by suramin up to 95%. In vivo, all controls developed extensive tumor growth and spread. No tumor was detectable in half of the suramin-treated animals after 8 weeks; tumor dissemination was almost completely depressed. Suramin therapy resulted in a complete regression of tumor macrovessels and a significant reduction of microvessel density.
Suramin significantly reduces primary tumor growth and dissemination in a clinically relevant rat model of pancreatic cancer and seems to play an important role for the inhibition of tumor angiogenesis.
我们在具有免疫活性的胰腺癌原位大鼠模型中研究了苏拉明对肿瘤生长和扩散的影响，并通过活体显微镜检查分析了肿瘤血管系统。
在体外，将大鼠胰腺导管癌细胞（DSL-6A）与苏拉明（10-800微克/毫升）一起孵育，并评估细胞增殖情况。在体内，在Lewis大鼠的胰腺中诱导产生DSL-6A肿瘤。动物接受苏拉明（60毫克/千克，每周腹腔注射）或赋形剂（对照组）。3天后开始治疗。在第1、4和8周进行活体显微镜检查，对肿瘤血管的直径、密度和通透性进行量化。在尸检时确定原发性肿瘤体积、局部浸润和转移扩散情况。通过免疫组织化学分析微血管密度。
在体外，苏拉明可将增殖抑制高达95%。在体内，所有对照组均出现广泛的肿瘤生长和扩散。8周后，一半接受苏拉明治疗的动物未检测到肿瘤；肿瘤扩散几乎完全受到抑制。苏拉明治疗导致肿瘤大血管完全消退，微血管密度显著降低。
在具有临床相关性的胰腺癌大鼠模型中，苏拉明显著降低原发性肿瘤的生长和扩散，并且似乎在抑制肿瘤血管生成中发挥重要作用。
