Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China.
Department of Pathology, Binhaiwan Central Hospital of Dongguan, Dongguan, China.
Dokl Biochem Biophys. 2024 Aug;517(1):285-290. doi: 10.1134/S1607672924600283. Epub 2024 Jul 13.
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.
贝伐珠单抗（bevacizumab，BEV）的直接抗肿瘤作用一直存在争议。药物直接抗肿瘤活性的证据主要来自体外实验，这些实验受到实验条件的极大影响。在这项研究中，我们评估了 BEV 含药培养基更新对 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 BEV 含药培养基更新的实验之间存在明显不同的结果。具体来说，在及时更换 BEV 含药培养基的情况下，BEV 抑制肿瘤细胞生长，但不进行培养基更新则促进肿瘤细胞生长。同时，与对照组相比，未进行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）明显积累，但更换培养基的组中则没有。此外，bFGF 中和部分逆转了培养基中未更新组中 BEV 的促增殖作用，而外源性 bFGF 则减弱了培养基更新组中 BEV 对肿瘤细胞生长的抑制作用。我们的数据从肿瘤细胞中自分泌细胞因子的补偿作用的角度解释了不同研究中关于 BEV 直接抗肿瘤作用的争议。
