Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, ROC.
Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan, ROC.
Int J Med Sci. 2021 Apr 22;18(11):2417-2430. doi: 10.7150/ijms.54468. eCollection 2021.
Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract and . The results showed that CAt extract greatly suppressed GBM cells both and and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G/G phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs and . CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future.
胶质母细胞瘤（GBM）是人类最常见的恶性原发性脑肿瘤，表现出高度浸润性生长和对传统化疗药物的耐药性。（CAt）提取物已被证明可以减轻术后疼痛并抑制 K562 白血病细胞的生长。本研究旨在评估 CAt 提取物对 GBM 的抗活性及其分子机制。结果表明，CAt 提取物在体外和体内均能显著抑制 GBM 细胞的生长，并提高荷瘤动物模型的存活率。此外，CAt 提取物增加了 ROS 水平并诱导 DNA 损伤，导致细胞周期阻滞在 G0/G1 期和细胞凋亡。Western blot 结果表明，CAt 提取物调节 p53/p21 和 CDK4/cyclin D1 蛋白表达，并激活外源性和内源性细胞凋亡。此外，CAt 提取物通过联合治疗增强了替莫唑胺的细胞毒性并降低了 AKT/mTOR 信号通路。在毒性试验中，CAt 提取物对正常细胞或器官表现出低细胞毒性。CAt 提取物通过诱导遗传毒性和激活细胞凋亡来抑制 GBM 的生长。本研究结果提示，CAt 提取物有望开发成为未来 GBM 治疗的治疗剂或辅助剂。
