Long Yan, Luo Xin-Jun, Zou Bo, Dai Xin-Jun, Fu Fang-Zhi, Wang Biao, Wu Li-Tong, Wu Yong-Rong, Zhou Qing, Tian Xue-Fei
Department of Andrology, the First Affiliated Hospital of Hunan University of Chinese Medicine Changsha 410007, China Hunan Provincial Key Laboratory of Traditional Chinese Medicine Prescription and Transformation, Hunan University of Chinese Medicine Changsha 410208, China Key Laboratory of Tumor Prevention Mechanism of Traditional Chinese Medicine,Hunan University of Chinese Medicine Changsha 410208, China.
Department of Andrology, the First Affiliated Hospital of Hunan University of Chinese Medicine Changsha 410007, China.
Zhongguo Zhong Yao Za Zhi. 2024 Dec;49(23):6378-6388. doi: 10.19540/j.cnki.cjcmm.20240909.401.
Based on the focal adhesion kinase(FAK)/steroid receptor coactivator(Src)/extracellular regulated protein kinase(ERK) pathway, this study explored the effects of Xihuang Pills on angiogenesis, invasion, and metastasis in prostate cancer. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to analyze and identify the active ingredients of Xihuang Pills. Bioinformatics techniques, including R language and Perl programs, were employed to analyze the interactions between prostate cancer-related targets and the potential targets of Xihuang Pills. A subcutaneous transplantation tumor model of prostate cancer was established in nude mice using PC3 cells to verify the efficacy and molecular mechanisms of Xihuang Pills. In vitro cellular experiments, including cell proliferation assays(CCK-8), Transwell assays, scratch assays, real-time quantitative reverse transcription PCR, and Western blot, were used to detect the effects of Xihuang Pills on the proliferation, invasion, and migration of prostate cancer cells, as well as on FAK/Src/ERK pathway-related targets. LC-MS/MS identified 99 active ingredients in Xihuang Pills, including gallic acid, gentisic acid, artemisinin, corilagin, phenylbutazone-glucoside, thujic acid, and arecoic acid B. Network pharmacological analysis of the active ingredients in Xihuang Pills revealed that the FAK/Src/ERK signaling pathway was a key pathway in its anti-prostate cancer effects. In vivo and in vitro experiments confirmed that Xihuang Pills significantly inhibited the proliferation, invasion, and migration of PC3 and LNCaP cells, suppressed the growth of PC3 subcutaneous tumors, and reduced the protein expression levels related to the FAK/Src/ERK signaling pathway. In conclusion, the inhibition of angiogenesis, invasion, and metastasis by regulating the FAK/Src/ERK pathway is one of the mechanisms by which Xihuang Pills exert anti-prostate cancer effects.
基于黏着斑激酶(FAK)/类固醇受体共激活因子(Src)/细胞外调节蛋白激酶(ERK)通路,本研究探讨了西黄丸对前列腺癌血管生成、侵袭和转移的影响。采用液相色谱-串联质谱法(LC-MS/MS)分析并鉴定西黄丸的活性成分。运用包括R语言和Perl程序在内的生物信息学技术分析前列腺癌相关靶点与西黄丸潜在靶点之间的相互作用。使用PC3细胞在裸鼠中建立前列腺癌皮下移植瘤模型,以验证西黄丸的疗效和分子机制。体外细胞实验,包括细胞增殖检测(CCK-8)、Transwell检测、划痕实验、实时定量逆转录PCR和蛋白质免疫印迹法,用于检测西黄丸对前列腺癌细胞增殖、侵袭和迁移以及FAK/Src/ERK通路相关靶点的影响。LC-MS/MS鉴定出西黄丸中的99种活性成分,包括没食子酸、龙胆酸、青蒿素、柯里拉京、保泰松葡萄糖苷、崖柏酸和槟榔次碱B。对西黄丸活性成分的网络药理学分析表明,FAK/Src/ERK信号通路是其抗前列腺癌作用的关键通路。体内和体外实验证实,西黄丸显著抑制PC3和LNCaP细胞的增殖、侵袭和迁移,抑制PC3皮下肿瘤的生长,并降低与FAK/Src/ERK信号通路相关的蛋白表达水平。总之,通过调节FAK/Src/ERK通路抑制血管生成、侵袭和转移是西黄丸发挥抗前列腺癌作用的机制之一。