Kuhn Hartmut, Köpff Carmen, Konrad Jana, Riedel Alexander, Gessner Christian, Wirtz Hubert
Division of Respiratory and Critical Care Medicine, Department of Medicine I, University of Leipzig, Johannisallee 32, Leipzig 04103, Germany.
Lung Cancer. 2004 May;44(2):167-74. doi: 10.1016/j.lungcan.2003.11.005.
Basic fibroblast growth factor (bFGF) is closely involved in angiogenesis and tumor growth of various cancers, but its role in proliferation and differentiation of non-small cell lung cancer (NSCLC) remains to be defined. The majority of NSCLC cell lines produce elevated protein levels of bFGF but do not secrete comparable amounts. We therefore investigated the influence of bFGF on the proliferation of three human NSCLC cell lines. Our experiments demonstrate that intracellular bFGF level and bFGF mRNA expression correlated with the proliferation rate in all three cell lines. Delivery of a bFGF neutralizing monoclonal antibody, anti-sense oligonucleotides or a vector expressing bFGF antisense cDNA into the cells inhibited tumor cell growth. Delivery of recombinant bFGF into a bFGF-negative cell line led to increased proliferation. These findings suggest that bFGF stimulates the growth of tumor cells by intracrine mechanisms. Strategies to inhibit bFGF in NSCLC may therefore be a promising approach in NSCLC therapy.
碱性成纤维细胞生长因子(bFGF)与多种癌症的血管生成和肿瘤生长密切相关,但其在非小细胞肺癌(NSCLC)增殖和分化中的作用仍有待确定。大多数NSCLC细胞系产生的bFGF蛋白水平升高,但分泌量却不相当。因此,我们研究了bFGF对三种人NSCLC细胞系增殖的影响。我们的实验表明,在所有三种细胞系中,细胞内bFGF水平和bFGF mRNA表达与增殖率相关。向细胞中递送bFGF中和单克隆抗体、反义寡核苷酸或表达bFGF反义cDNA的载体可抑制肿瘤细胞生长。将重组bFGF递送至bFGF阴性细胞系可导致增殖增加。这些发现表明,bFGF通过自分泌机制刺激肿瘤细胞生长。因此,在NSCLC中抑制bFGF的策略可能是NSCLC治疗中一种有前景的方法。