[Effects of Xihuang Pills on angiogenesis, invasion, and metastasis of p rostate cancer based on FAK/Src/ERK pathway].

Q3 Pharmacology, Toxicology and Pharmaceutics Zhongguo Zhongyao Zazhi Pub Date : 2024-12-01 DOI:10.19540/j.cnki.cjcmm.20240909.401
Yan Long, Xin-Jun Luo, Bo Zou, Xin-Jun Dai, Fang-Zhi Fu, Biao Wang, Li-Tong Wu, Yong-Rong Wu, Qing Zhou, Xue-Fei Tian
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Abstract

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.

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[西黄丸基于FAK/Src/ERK通路对前列腺癌血管生成、侵袭和转移的影响]。
本研究基于局灶黏附激酶(FAK)/类固醇受体共激活因子(Src)/细胞外调节蛋白激酶(ERK)通路,探讨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)对西黄丸的有效成分进行分析鉴定。采用生物信息学技术,包括R语言和Perl程序,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。利用PC3细胞建立裸鼠前列腺癌皮下移植肿瘤模型,验证西黄丸的疗效及分子机制。体外细胞实验采用细胞增殖法(CCK-8)、Transwell法、scratch法、实时定量反转录PCR法、Western blot法检测西黄丸对前列腺癌细胞增殖、侵袭、迁移的影响,以及对FAK/Src/ERK通路相关靶点的影响。LC-MS/MS鉴定出西黄丸中99种有效成分,包括没食子酸、龙胆酸、青蒿素、芫花素、苯丁酮-葡萄糖苷、枸杞酸、槟榔酸b。对西黄丸有效成分进行网络药理分析,发现FAK/Src/ERK信号通路是其抗前列腺癌的关键通路。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,降低FAK/Src/ERK信号通路相关蛋白的表达水平。综上所述,通过调控FAK/Src/ERK通路抑制血管生成、侵袭和转移是西黄丸抗前列腺癌作用的机制之一。
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来源期刊
Zhongguo Zhongyao Zazhi
Zhongguo Zhongyao Zazhi Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.50
自引率
0.00%
发文量
581
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