Digestive System Department, First Affiliated Hospital of Gannan Medical University, Ganzhou, People's Republic of China.
School of Medical & Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Cell Biochem Funct. 2020 Aug;38(6):702-709. doi: 10.1002/cbf.3537. Epub 2020 Apr 13.
Gastric cancer (GC) is one of the most prevalent types of malignancies. Betulinic acid (BA) is a natural pentacyclic triterpene with a lupine structure. However, to the best of our knowledge, there is no research study on the anti-tumour and anti-metastasis effect of BA on GC. In this study, we assessed the anti-cancer effect of BA on human GC cells in vitro and in vivo. We first investigated the cytotoxicity and anti-proliferation effect of BA on GC cells of SNU-16 and NCI-N87. The results indicated that BA had significant cytotoxic and inhibitory effects on GC cells in a dose- and time-dependent manner. To further study the cytotoxic action of BA on GC cells, we assessed the apoptotic induction effect of BA on SNU-16 cells and found that BA distinctly induced apoptosis in SNU-16 cells. In addition, BA inhibited the migratory and invasive abilities of SNU-16 cells. Western-blot analysis revealed that BA suppressed the migration and invasion of GC cells by impairing epithelial-mesenchymal transition progression. Furthermore, in vivo experiments showed that BA could delay tumour growth and inhibit pulmonary metastasis, which is consistent with the results of in vitro studies. Overall, we evaluated the anti-cancer effect of BA on human GC cells in vivo and in vitro, and the present study provides new evidence on the use of BA as a potential anti-cancer drug for GC treatment. SIGNIFICANCE OF THE STUDY: BA significantly suppressed proliferation and triggered apoptosis in GC cells. Additionally, BA remarkably inhibited migration and invasion of GC cells by impairing the epithelial-mesenchymal transition signalling pathway. It is worth noting that BA drastically retarded tumour growth in the xenograft mouse model of GC. Our results indicated that BA can be considered a candidate drug for GC therapy.
胃癌（GC）是最常见的恶性肿瘤类型之一。白桦酸（BA）是一种具有羽扇豆结构的天然五环三萜。然而，据我们所知，目前还没有关于 BA 对 GC 的抗肿瘤和抗转移作用的研究。在本研究中，我们评估了 BA 对体外和体内人 GC 细胞的抗癌作用。我们首先研究了 BA 对 SNU-16 和 NCI-N87 GC 细胞的细胞毒性和抗增殖作用。结果表明，BA 对 GC 细胞具有显著的剂量和时间依赖性细胞毒性和抑制作用。为了进一步研究 BA 对 GC 细胞的细胞毒性作用，我们评估了 BA 对 SNU-16 细胞的诱导凋亡作用，发现 BA 明显诱导 SNU-16 细胞凋亡。此外，BA 抑制 SNU-16 细胞的迁移和侵袭能力。Western-blot 分析表明，BA 通过抑制上皮-间充质转化（EMT）进程来抑制 GC 细胞的迁移和侵袭。此外，体内实验表明，BA 可延缓肿瘤生长并抑制肺转移，这与体外研究结果一致。总之，我们评估了 BA 对体内和体外人 GC 细胞的抗癌作用，本研究为将 BA 用作 GC 治疗的潜在抗癌药物提供了新的证据。
BA 显著抑制 GC 细胞的增殖并触发其凋亡。此外，BA 通过抑制 EMT 信号通路显著抑制 GC 细胞的迁移和侵袭。值得注意的是，BA 明显延缓了 GC 异种移植小鼠模型中的肿瘤生长。我们的结果表明，BA 可被视为 GC 治疗的候选药物。
