Engineering Research Center for Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi 214122, China; JITRI Future Food Technol Res Inst Co Ltd, Yixing 214200, China.
School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.
Biomed Pharmacother. 2024 Oct;179:117423. doi: 10.1016/j.biopha.2024.117423. Epub 2024 Sep 10.
Hepatocellular carcinoma (HCC), a hypervascular tumor, is the most frequent primary malignant tumor of the liver. Angiogenesis inhibitors, such as endogenous angiogenesis inhibitors, are essential for HCC therapy and have generated significant interest owing to their safety, efficacy, and multitargeting attributes. Canstatin is an angiogenesis inhibitor derived from the basement membrane and exerts anti-tumor effects. However, the inhibitory effects and underlying mechanisms of action of canstatin on HCC remain unclear. Therefore, in this study, HepG2 and Huh7 cells were used to investigate the inhibitory effects of recombinant canstatin on HCC cells. Subsequently, the biosafety and inhibitory effects of recombinant canstatin on tumor growth were investigated in a xenograft animal model of liver cancer. Canstatin inhibited the growth of liver cancer cells by regulating their proliferation, apoptosis, and migration. Additionally, it suppressed the occurrence and progression of HCC by modulating the HIF-1α/VEGF signaling pathway. In mice, canstatin exerted no discernible harmful side effects and suppressed the growth of HCC subcutaneous xenograft tumors. Overall, our findings shed light on the molecular pathways underlying canstatin-induced HCC cell death that may help develop novel HCC treatments.
肝细胞癌（HCC）是一种富血管肿瘤，是肝脏最常见的原发性恶性肿瘤。血管生成抑制剂，如内源性血管生成抑制剂，是 HCC 治疗的关键，由于其安全性、疗效和多靶向特性，引起了广泛关注。Canstatin 是一种来源于基底膜的血管生成抑制剂，具有抗肿瘤作用。然而，Canstatin 对 HCC 的抑制作用及其作用机制尚不清楚。因此，在本研究中，我们使用 HepG2 和 Huh7 细胞来研究重组 Canstatin 对 HCC 细胞的抑制作用。随后，在肝癌异种移植动物模型中研究了重组 Canstatin 的生物安全性和对肿瘤生长的抑制作用。Canstatin 通过调节肝癌细胞的增殖、凋亡和迁移来抑制其生长。此外，它通过调节 HIF-1α/VEGF 信号通路抑制 HCC 的发生和发展。在小鼠中，Canstatin 没有产生明显的有害副作用，并抑制了 HCC 皮下异种移植肿瘤的生长。总之，我们的研究结果揭示了 Canstatin 诱导 HCC 细胞死亡的分子途径，这可能有助于开发新的 HCC 治疗方法。
