Abstract：
The direct antitumor effect of bevacizumab (BEV) has long been debated. Evidence of the direct antitumor activities of drugs are mainly obtained from in vitro experiments, which are greatly affected by experimental conditions. In this study, we evaluated the effect of BEV-containing medium renewal on the results of in vitro cytotoxicity experiments in A549 and U251 cancer cells. We observed starkly different results between the experiments with and without BEV-containing medium renewal. Specifically, BEV inhibited the tumor cell growth in the timely replacement with a BEV-containing medium but promoted tumor cell growth without medium renewal. Meanwhile, compared with the control, a significant basic fibroblast growth factor (bFGF) accumulation in the supernatant was observed in the group without medium renewal but none in that with replaced medium. Furthermore, bFGF neutralization partially reversed the pro-proliferative effect of BEV in the medium non-renewed group, while exogenous bFGF attenuated the tumor cell growth inhibition of BEV in the medium-renewed group. Our data explain the controversy over the direct antitumor effect of BEV in different studies from the perspective of the compensatory autocrine cytokines in tumor cells.
摘要：
贝伐单抗（BEV）的直接抗肿瘤作用长期以来一直存在争议。药物直接抗肿瘤活性的证据主要来自体外实验,受实验条件的影响很大。在这项研究中,我们评估了含BEV的培养基更新对A549和U251癌细胞体外细胞毒性实验结果的影响。我们观察到有和没有含BEV的培养基更新的实验结果截然不同。具体来说,在用含BEV的培养基及时替换时,BEV抑制肿瘤细胞生长,但在没有培养基更新的情况下促进肿瘤细胞生长。同时,与对照组相比，在没有培养基更新的组中，观察到上清液中碱性成纤维细胞生长因子（bFGF）的显着积累，但在更换培养基的组中没有。此外，bFGF中和部分逆转了BEV在中等非更新组中的促增殖作用，而外源性bFGF减弱了BEV对中等更新组肿瘤细胞生长的抑制作用。我们的数据从肿瘤细胞中代偿性自分泌细胞因子的角度解释了BEV在不同研究中直接抗肿瘤作用的争议。
