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.

南蛇藤茎中的萜烯提取物通过调节 PTBP1 和 ACTN4 之间的蛋白质相互作用来抑制胃癌细胞中的肌动蛋白细胞骨架重塑。

Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4.

发表日期:2024 Aug
作者: Zewen Chu, Miao Zhu, Yuanyuan Luo, Yaqi Hu, Xinyi Feng, Jiacheng Shen, Haibo Wang, Masataka Sunagawa, Yanqing Liu
来源: Journal of Pharmaceutical Analysis

摘要:

辅助放化疗、分子靶向治疗和免疫治疗经常用于延长晚期胃癌(GC)患者的生存期。然而,这些治疗方法大多具有毒副作用、耐药性,并且对生存和生活质量的改善有限。因此,发现和开发高效且毒性最小的针对GC的新药物至关重要。在之前的研究中,南蛇藤茎中的总萜提取物表现出抗GC活性;但具体机制尚不清楚。我们的研究利用免疫共沉淀质谱 (Co-IP-MS)、聚嘧啶束结合蛋白 1 (ptbp1) 规则间隔短回文重复相关蛋白 9 (Cas9) 敲除 (KO) 小鼠模型、组织微阵列和功能实验表明 α actinin-4 (ACTN4) 可能是 GC 的重要生物标志物。 PTBP1 通过与 ACTN4 相互作用影响 GC 细胞中肌动蛋白细胞骨架的重组。南蛇藤茎提取物 (COE) 可能直接靶向 ACTN4,影响 PTBP1 和 ACTN4 之间的相互作用,从而发挥抗 GC 作用。© 2024 作者。
Adjuvant chemoradiotherapy, molecular targeted therapy, and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer (GC). However, most of these treatments have toxic side effects, drug resistance, and limited improvements in survival and quality of life. Therefore, it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity. In previous studies, the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity; however, the specific mechanism was unclear. Our research utilising co-immunoprecipitation-mass spectrometry (Co-IP-MS), polypyrimidine tract binding protein 1 (ptbp1) clustered regularly interspaced short palindromic repeat-associated protein 9 (Cas9)-knockout (KO) mouse model, tissue microarray, and functional experiments suggests that alpha actinin-4 (ACTN4) could be a significant biomarker of GC. PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4. Celastrus orbiculatus stem extract (COE) may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4, thereby exerting anti-GC effects.© 2024 The Author(s).