Zhang Min, Dai Zhi, Zhao Xudong, Wang Gan, Lai Ren
Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology - The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Kunming, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
Front Oncol. 2021 Aug 2;11:715673. doi: 10.3389/fonc.2021.715673. eCollection 2021.
Glioma is the most common form of malignant brain cancer. It is very difficult to cure malignant glioma because of the presence of glioma stem cells, which are a barrier to cure, have high tumorigenesis, associated with drug resistance, and responsible for relapse by regulating stemness genes. In this study, our results demonstrated that anticarin β, a natural compound from , can effectively and selectively suppress proliferation and cause apoptosis in glioma cells, which has an IC that is 100 times lower than that in mouse normal neural stem cells. Importantly, cell sphere formation assay and real time-quantitative analysis reveal that anticarin β inhibits cancer stemness by modulating related stemness gene expression. Additionally, anticarin β induces DNA damage to regulate the oncogene expression of signal transducer and activator of transcription 3 (STAT3), Akt, mitogen-activated protein kinases (MAPKs), and eventually leading to apoptosis. Furthermore, anticarin β effectively inhibits glioma growth and prolongs the lifts pan of tumor-bearing mice without systemic toxicity in the orthotopic xenograft mice model. These results suggest that anticarin β is a promising candidate inhibitor for malignant glioma.
神经胶质瘤是恶性脑癌最常见的形式。由于神经胶质瘤干细胞的存在，恶性神经胶质瘤很难治愈，这些干细胞是治愈的障碍，具有高肿瘤发生能力，与耐药性相关，并通过调节干性基因导致复发。在本研究中，我们的结果表明，来自[具体来源未提及]的天然化合物抗癌素β能有效且选择性地抑制神经胶质瘤细胞增殖并诱导其凋亡，其半数抑制浓度（IC）比小鼠正常神经干细胞低100倍。重要的是，细胞球形成试验和实时定量分析表明，抗癌素β通过调节相关干性基因表达来抑制癌症干性。此外，抗癌素β诱导DNA损伤以调节信号转导和转录激活因子3（STAT3）、Akt、丝裂原活化蛋白激酶（MAPK）的癌基因表达，最终导致细胞凋亡。此外，在原位异种移植小鼠模型中，抗癌素β有效抑制神经胶质瘤生长并延长荷瘤小鼠的生存期，且无全身毒性。这些结果表明，抗癌素β是一种有前景的恶性神经胶质瘤候选抑制剂。
