Zhang Qiuping, Huang Qiuju, Cheng Zhiping, Xue Wei, Liu Shoushi, Liao Yunnuo, Li Xiaolan, Chen Xin, Han Yaoyao, Zhu Dan, Su Zhiheng, Yang Xin, Luo Zhuo, Guo Hongwei
Department of Traditional Chinese Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, Nanning 530021, China; Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, Guangxi Medical University, Nanning 530021, China.
Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
Chin J Nat Med. 2025 Jan;23(1):64-76. doi: 10.1016/S1875-5364(25)60804-1.
Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
消癌平注射液具有抗前列腺癌（PCa）的作用，但其潜在机制尚不清楚。本研究旨在探讨消癌平对前列腺癌的影响并阐明其作用机制。使用细胞计数试剂盒-8（CCK-8）法评估前列腺癌细胞增殖。通过Hoechst染色和蛋白质免疫印迹法评估细胞凋亡。采用蛋白质组学技术鉴定消癌平在前列腺癌细胞中调节的关键分子和重要信号通路。为了进一步验证潜在的关键基因和重要通路，进行了一系列实验，包括吖啶橙（AO）染色、透射电子显微镜检查和免疫荧光测定。使用PC3异种移植小鼠模型研究消癌平在体内抗前列腺癌的分子机制。结果表明，消癌平显著抑制多种前列腺癌细胞系的细胞增殖。在C4-2和前列腺癌细胞系-3（PC3）细胞中，消癌平诱导细胞凋亡，表现为B细胞淋巴瘤-2（Bcl-2）水平降低和Bcl-2相关X蛋白（Bax）水平升高。蛋白质组学、免疫荧光和定量逆转录-聚合酶链反应（qRT-PCR）研究表明，叉头框O3a（FoxO3a）自噬降解与消癌平的抗前列腺癌作用密切相关。消癌平通过降低自噬相关蛋白5（Atg5）/自噬相关蛋白12（Atg12）的表达水平并增强FoxO3a的表达和核转位来阻碍自噬。此外，消癌平在PC3异种移植小鼠中表现出强大的抗前列腺癌作用，并在肿瘤组织中触发FoxO3a核转位现象。这些发现表明，消癌平通过抑制FoxO3a自噬降解诱导前列腺癌细胞凋亡，这可能为消癌平注射液作为前列腺癌的有效抗癌疗法提供新的视角。
