Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

中文翻译：

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臭椿衍生的臭椿通过下调 p23 表达诱导抑制碱基切除修复来增强胃癌细胞凋亡

化疗在胃癌的治疗中发挥着不可替代的作用，但目前可用的化疗药物并不理想。药用植物的应用是新药发现的重要方向。通过对GC类器官的药物筛选，我们确定了茴香酮在体外和体内对GC细胞具有抗癌作用. 我们还发现 AIL 可以诱导 GC 细胞中的 DNA 损伤和凋亡。进一步对PDX组织进行转录组测序表明，AIL抑制了在DNA损伤修复中起重要作用的XRCC1的表达，该结果也通过western blotting得到证实。此外，我们发现AIL抑制了P23的表达，抑制P23降低了XRCC1的表达，表明AIL可以通过P23调节XRCC1。免疫共沉淀结果表明AIL可以抑制P23和XRCC1与HSP90的结合。这些发现表明 AIL 可以诱导 GC 细胞中的 DNA 损伤和凋亡。同时，AIL可以通过下调P23的表达来降低XRCC1的活性，从而抑制DNA损伤修复。