研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

羌活提取物通过防止结肠直肠癌中 BIM 的降解来促进细胞凋亡。

Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer.

发表日期:2024 Jul 05
作者: Jun-He Chen, Cheng-Ming Wei, Qian-Yu Lin, Zi Wang, Fu-Ming Zhang, Mei-Na Shi, Wen-Jian Lan, Chang-Gang Sun, Wan-Jun Lin, Wen-Zhe Ma
来源: Cell Death & Disease

摘要:

结直肠癌(CRC)是一种世界范围内普遍存在的恶性肿瘤,促使人们对抗癌药物进行广泛的研究。传统中药材因其多样化的药理活性而为癌症治疗提供了有前景的途径。本研究探讨中药羌活(QH)对CRC细胞的影响及其潜在机制。采用磺基罗丹明B法和集落形成实验评估羌活提取物对CRC细胞增殖的影响。 HCT116 和 Caco-2 系。利用碘化丙啶 (PI) 染色检测细胞周期进展,使用 PE 膜联蛋白 V 染色检测细胞凋亡。采用蛋白质印迹法检测凋亡蛋白的水平,包括 B 细胞淋巴瘤 2 相互作用细胞死亡介质 (BIM)、B 细胞淋巴瘤 2 (Bcl-2)、Bcl-2 相关 X 蛋白 (BAX) 和裂解的 caspase-3,以及用蛋白质合成抑制剂放线菌酮处理后的 BIM 稳定性。使用慢病毒介导的 shRNA 抑制 BAX 的表达,以验证 BIM/BAX 轴参与 QH 诱导的细胞凋亡。使用异种移植模型观察 QH 提取物对肿瘤生长的体内影响。最后,使用 APCMin 小鼠研究 QH 提取物对原发性肠道肿瘤的影响。 QH 提取物在体外表现出显着的抗 CRC 活性,这通过抑制细胞增殖、扰乱细胞周期进程和诱导细胞凋亡来证明。从机制上讲,QH 提取物显着提高了 BIM 蛋白的稳定性,BIM 蛋白在无压力条件下会快速降解。 BIM 下游效应子 BAX 的敲低可显着挽救 QH 诱导的细胞凋亡。此外,QH 提取物的体外效果在体内得到重现。 QH 提取物显着抑制裸鼠 HCT116 异种移植瘤的肿瘤生长,并减少 APCMin 小鼠肠息肉的数量。QH 提取物通过阻止 BIM 降解促进 CRC 细胞凋亡。© 2024. 华中科技大学。
Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism.The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors.QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice.QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.© 2024. Huazhong University of Science and Technology.