Department of Radiotherapy, Qingdao Jiaozhou City Central Hospital, Jiaozhou, Qingdao 266300, P.R. China.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12068. Epub 2021 Apr 13.
Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy worldwide with poor prognosis and high metastasis and recurrence rates. Although apatinib has been demonstrated to have potential antitumor activity in multiple solid tumors, the underlying mechanism of apatinib in HCC treatment remains to be elucidated. In the present study, apatinib were used to treat HCC cells transfected with or without VEGFR2 overexpression vectors. The proliferation of HCC cells was detected by MTT assay. The migration and invasion of HCC cells were detected by wound healing assay and Transwell assay. The ability of angiogenesis of HCC cells were detected by tube formation assay. The related protein expression levels were detected by western blotting. The present study aims to investigate the effect and potential mechanism of apatinib on the migration, invasion and angiogenesis of HCC cells. It was found that apatinib treatment significantly inhibited the proliferation, migration and invasion of Hep3b cells and suppressed angiogenesis in HUVECs. In addition, apatinib inhibited the epithelial‑mesenchymal transition of Hep3b cells by increasing the expression of the epithelial hallmarks E‑cadherin and α‑catenin and decreased the expression of the mesenchymal hallmarks N‑cadherin and vimentin. These effects were associated with the downregulation of VEGF and VEGFR2 and suppression of the PI3K/AKT signaling pathway. Thus, apatinib inhibited cell migration, invasion and angiogenesis by blocking the VEGF and PI3K/AKT pathways, supporting an effective therapeutic strategy in the treatment of HCC.
肝细胞癌 (HCC) 是一种在全球范围内常见的恶性肿瘤，预后不良，转移和复发率高。虽然阿帕替尼已被证明在多种实体瘤中具有潜在的抗肿瘤活性，但阿帕替尼治疗 HCC 的潜在机制仍有待阐明。本研究采用阿帕替尼处理转染或未转染 VEGFR2 过表达载体的 HCC 细胞，MTT 法检测 HCC 细胞的增殖，划痕愈合实验和 Transwell 实验检测 HCC 细胞的迁移和侵袭，管腔形成实验检测 HCC 细胞的血管生成能力，Western blot 检测相关蛋白表达水平。本研究旨在探讨阿帕替尼对 HCC 细胞迁移、侵袭和血管生成的作用及其潜在机制。结果发现，阿帕替尼处理显著抑制 Hep3b 细胞的增殖、迁移和侵袭，并抑制 HUVECs 的血管生成。此外，阿帕替尼通过增加上皮标志物 E-钙黏蛋白和α-连环蛋白的表达，降低间充质标志物 N-钙黏蛋白和波形蛋白的表达，抑制 Hep3b 细胞的上皮-间充质转化。这些作用与 VEGF 和 VEGFR2 的下调以及 PI3K/AKT 信号通路的抑制有关。因此，阿帕替尼通过阻断 VEGF 和 PI3K/AKT 通路抑制细胞迁移、侵袭和血管生成，为 HCC 的治疗提供了一种有效的治疗策略。
