Exploring the mechanism of Xiaoaiping Injection inhibiting autophagy in prostate cancer based on proteomics
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ZHANG Qiuping,
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HUANG Qiuju,
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CHENG Zhiping,
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XUE Wei,
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LIU Shoushi,
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LIAO Yunnuo,
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LI Xiaolan,
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CHEN Xin,
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HAN Yaoyao,
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ZHU Dan,
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SU Zhiheng,
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YANG Xin,
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LUO Zhuo,
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GUO Hongwei
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Graphical Abstract
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Abstract
Xiaoaiping (XAP) Injection exhibits the anti-prostate cancer (PCa) effect, but the underlying mechanism is still obscure. This study aims to examine the influence of XAP on PCa and determine its underlying mechanism. The proliferation of PCa cells was assessed via CCK-8 assay. Hoechst staining and Western blotting were conducted to determine cell apoptosis. The key molecules and significant signaling pathways modulated by XAP in PCa cells were subsequently studied utilizing proteomics technology. To further verify the potential key genes and important pathways, we performed a series of assays, including acridine orange (AO) staining, transmission electron microscopy, immunofluorescence assays and so on. Finally, the molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mice model. The cell proliferation of multiple PCa cell lines was shown to be substantially inhibited by XAP. In C4-2 and PC3 cells, XAP could induce cellular apoptotic, as evidenced by elevated Bax levels and reduced Bcl-2 levels. Proteomic, immunofluorescence, and qRT-PCR investigations demonstrated a strong link between FoxO3a’s autophagic degradation and the anti-PCa action of XAP. By lowering the expression levels of Atg5/Atg12 and enhancing FoxO3a expression and nuclear translocation, XAP hindered autophagy. Additionally, XAP in PC3 xenograft mice displayed strong anti-PCa action and triggered FoxO3a’s nuclear translocation in tumor tissue. Our results indicate that XAP induces PCa apoptosis via inhibiting the FoxO3a autophagic degradation, which might offer a fresh perspective on XAP injection’s potential as an effective new anti-cancer therapy for PCa.
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