背景：有效治疗影响全球男性健康的前列腺癌（PCa）仍然是一个挑战。由于化疗的严重毒副作用，寻找天然替代药物并探索其抗肿瘤机制至关重要。
方法：通过网络药理学分析靶点和信号通路，并通过分子对接和LC-MS进行验证。扩散,凋亡，入侵,CCK-8法检测DU145细胞的迁移,流式细胞术,还有Transwell,分别。Westernblot检测Bcl-2、caspase-3、CXCL12和CXCR4的表达和Akt1的磷酸化。应用Akt1过表达来鉴定Akt1相关CXCL12/CXCR4途径在调节PCa中的参与。进行裸鼠肿瘤发生以分析槲皮素对体内PCa的影响。
结果：网络药理学结果显示槲皮素是益肾通络解毒方的主要活性成分，Akt1是PCa的治疗靶点。LC-MS分析显示益肾通络解毒方中存在槲皮素,分子对接证明槲皮素与Akt1结合。槲皮素通过上调caspase-3和下调Bcl-2表达抑制DU145细胞增殖,促进细胞凋亡，降低侵袭和迁移能力。在体内,槲皮素通过Akt1相关的CXCL12/CXCR4通路下调CXCL12和CXCR4的表达并抑制PCa的发育。
结论：作为益肾通络解毒方的活性成分，槲皮素通过Akt1相关的CXCL12/CXCR4通路抑制PCa的发育。本研究为PCa的治疗提供了新的思路,为进一步的研究提供了理论依据。
BACKGROUND: It remains a challenge to effectively treat prostate cancer (PCa) that affects global men\'s health. It is essential to find a natural alternative drug and explore its antitumor mechanism due to the serious toxic side effects of chemotherapy.
METHODS: The targets and signaling pathways were analyzed by network pharmacology and verified by molecular docking and LC-MS. The proliferation, apoptosis, invasion, and migration of DU145 cells were detected by the CCK-8 method, flow cytometry, and Transwell, respectively. The Bcl-2, caspase-3, CXCL12, and CXCR4 expressions and Akt1 phosphorylation were determined by Western blot. Akt1 overexpression was applied to identify the involvement of the Akt1- related CXCL12/CXCR4 pathway in regulating PCa. Nude mouse tumorigenesis was performed to analyze the effect of quercetin on PCa in vivo.
RESULTS: Network pharmacology analysis displayed that quercetin was the main active component of the Yishen Tongluo Jiedu recipe and Akt1 was the therapy target of PCa. LC-MS analysis showed that quercetin existed in the Yishen Tongluo Jiedu recipe, and molecular docking proved that quercetin bound to Akt1. Quercetin inhibited the proliferation of DU145 cells by upregulating caspase-3 and downregulating Bcl-2 expression, promoting apoptosis and reducing invasion and migration abilities. In vivo, quercetin downregulated CXCL12 and CXCR4 expressions and inhibited PCa development by the Akt1-related CXCL12/CXCR4 pathway.
CONCLUSIONS: As the active component of the Yishen Tongluo Jiedu recipe, quercetin inhibited PCa development through the Akt1-related CXCL12/CXCR4 pathway. This study provided a new idea for PCa treatment and a theoretical basis for further research.
