Exploring the mechanism of Xiaoaiping Injection inhibiting autophagy in prostate cancer based on proteomics.
10.1016/S1875-5364(25)60804-1
- Author:
Qiuping ZHANG
1
;
Qiuju HUANG
2
;
Zhiping CHENG
2
;
Wei XUE
3
;
Shoushi LIU
3
;
Yunnuo LIAO
3
;
Xiaolan LI
3
;
Xin CHEN
3
;
Yaoyao HAN
3
;
Dan ZHU
2
;
Zhiheng SU
2
;
Xin YANG
4
;
Zhuo LUO
5
;
Hongwei GUO
6
Author Information
1. 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.
2. Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
3. 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.
4. Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, Guangxi Medical University, Nanning 530021, China. Electronic address: xiny1301@Hotmail.com.
5. Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, Nanning 530021, China. Electronic address: luozhuo@gxmu.edu.cn.
6. 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. Electronic address: hongweiguo@gxmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Autophagy;
Forkhead box O3a;
Prostate cancer;
Xiaoaiping Injection
- MeSH:
Male;
Humans;
Prostatic Neoplasms/physiopathology*;
Autophagy/drug effects*;
Animals;
Drugs, Chinese Herbal/pharmacology*;
Proteomics;
Mice;
Apoptosis/drug effects*;
Cell Line, Tumor;
Cell Proliferation/drug effects*;
Forkhead Box Protein O3/genetics*;
Xenograft Model Antitumor Assays;
Mice, Nude;
Mice, Inbred BALB C
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(1):64-76
- CountryChina
- Language:English
-
Abstract:
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.
