Chu Zewen, Zhu Miao, Luo Yuanyuan, Hu Yaqi, Feng Xinyi, Shen Jiacheng, Wang Haibo, Sunagawa Masataka, Liu Yanqing
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, China.
The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, Jiangsu, 225001, China.
J Pharm Anal. 2024 Aug;14(8):101021. doi: 10.1016/j.jpha.2024.101021. Epub 2024 Jun 13.
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 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 () 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. stem extract (COE) may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4, thereby exerting anti-GC effects.
辅助放化疗、分子靶向治疗和免疫治疗常用于延长晚期胃癌（GC）患者的生存期。然而，这些治疗大多具有毒副作用、耐药性，且在生存期和生活质量方面的改善有限。因此，发现和开发针对GC的高效且毒性最小的新药物至关重要。在先前的研究中，[植物名称]茎的总萜类提取物显示出抗GC活性；然而，具体机制尚不清楚。我们利用免疫共沉淀-质谱联用（Co-IP-MS）、多嘧啶序列结合蛋白1（PTBP1）、成簇规律间隔短回文重复序列相关蛋白9（Cas9）基因敲除（KO）小鼠模型、组织芯片和功能实验的研究表明，α-辅肌动蛋白-4（ACTN4）可能是GC的一个重要生物标志物。PTBP1通过与ACTN4相互作用影响GC细胞中的肌动蛋白细胞骨架重塑。[植物名称]茎提取物（COE）可能直接靶向ACTN4并影响PTBP1与ACTN4之间的相互作用，从而发挥抗GC作用。
