Key Laboratory of Medical Molecular Virology (NHC & MOE & CAMS), Institutes of Biomedical Sciences, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences,Shanghai Medical College, Fudan University, Shanghai 200032, China.
State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Jan 12;53(1):19-28. doi: 10.1093/abbs/gmaa139.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. At present, drug options for systemic treatment of HCC are very limited. There is an urgent need to develop additional effective drugs for HCC treatment. In the present study, we found that proscillaridin A (ProA), a cardiac glycoside, exerted a strong anticancer effect on multiple HCC cell lines. ProA significantly inhibited the cell proliferation, migration, and invasion of HCC cells. ProA also had a marked inhibitory effect on the progression of HCC in the MHCC97H xenograft nude mouse model. ProA-mediated suppression of HCC was closely related to cell apoptosis. ProA-treated HCC cells displayed significant mitochondrial damage and elevated reactive oxygen species production, resulting in profound cell apoptosis. Meanwhile, ProA also played a role in autophagy induction in HCC cells. Defects in autophagy partially relieved ProA's anticancer effect in HCC cells. Our findings demonstrate that ProA can effectively inhibit HCC progression and may serve as a potential therapeutic agent for HCC treatment.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。目前，用于 HCC 系统治疗的药物选择非常有限。迫切需要开发用于 HCC 治疗的其他有效药物。在本研究中，我们发现，地高辛（一种强心苷）对多种 HCC 细胞系具有很强的抗癌作用。ProA 显著抑制 HCC 细胞的增殖、迁移和侵袭。ProA 对 MHCC97H 异种移植裸鼠模型中的 HCC 进展也有显著的抑制作用。ProA 介导的 HCC 抑制与细胞凋亡密切相关。ProA 处理的 HCC 细胞显示出明显的线粒体损伤和活性氧产生的增加，导致严重的细胞凋亡。同时，ProA 还在 HCC 细胞中诱导自噬。自噬缺陷部分缓解了 ProA 对 HCC 细胞的抗癌作用。我们的研究结果表明，ProA 可以有效地抑制 HCC 的进展，可能成为 HCC 治疗的一种潜在治疗剂。
