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BASIC RESEARCH
Fuzheng Kang’ai decoction suppresses hepatocellular carcinoma via regulation of the KLF4/HIF-1α/CA9 signaling axis
1
Department of Pharmacy, Shaanxi Cancer Hospital, Xi’an, Shaanxi, China
2
Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, China
3
Department of Integrated Traditional Chinese and Western Medicine, Shaanxi Cancer Hospital, Xi’an, Shaanxi, China
4
Third Department of Internal Medicine, Shaanxi Cancer Hospital, Xi’an, Shaanxi, China
5
Department of Thoracic Surgery, Shaanxi Cancer Hospital, Xi’an, Shaanxi, China
6
Department of Scientific Research and Education, Shaanxi Cancer Hospital, Xi’an, Shaanxi, China
7
School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
These authors had equal contribution to this work
Submission date: 2025-11-07
Final revision date: 2025-12-22
Acceptance date: 2026-01-05
Online publication date: 2026-04-01
Corresponding author
Yili Zhang
Third Department of Internal Medicine Shaanxi Provincial Cancer Hospital No. 309 Yanta West Road Xi’an 710061 Shaanxi, China
Third Department of Internal Medicine Shaanxi Provincial Cancer Hospital No. 309 Yanta West Road Xi’an 710061 Shaanxi, China
Peixi Zhao
Department of Pharmacy Shaanxi Provincial Cancer Hospital No. 309 Yanta West Road Xi’an 710061 Shaanxi, China
Department of Pharmacy Shaanxi Provincial Cancer Hospital No. 309 Yanta West Road Xi’an 710061 Shaanxi, China
KEYWORDS
hepatocellular carcinomaFuzheng Kang’ai decoctiontraditional Chinese medicinephytochemicalsbioactive components
TOPICS
ABSTRACT
Introduction:
Clinical studies have established the efficacy of Fuzheng Kang’ai formula (FZKAF) in hepatocellular carcinoma (HCC) management. The molecular basis of FZKAF’s HCC-suppressive effects is not fully characterized. This investigation aimed to mechanistically delineate FZKAF’s therapeutic actions against HCC.
Material and methods:
Phytochemical characterization via liquid chromatography-mass spectrometry (LC-MS) established the decoction’s bioactive constituents. CCK-8 assays quantified proliferative suppression and cytotoxicity, while Annexin V-FITC/PI staining and cell cycle analysis mapped apoptosis induction. Integrated proteomic and transcriptomic profiling screened core targets and signaling pathways. Therapeutic efficacy was ultimately confirmed in an orthotopic HCC nude mouse model.
Results:
Phytochemical profiling identified 33 bioactive compounds in serum following FZKAF administration, including 9 established anti-tumor agents such as paeoniflorin, catechin, kaempferol, and quercetin. Functionally, FZKAF demonstrated dual anti-HCC efficacy by suppressing tumor growth in vivo and inhibiting 97H cell proliferation in vitro while promoting apoptosis through mitochondrial dysfunction. Mechanistic interrogation via multi-omics revealed FZKAF coordinately modulates KLF4, HIF-1a, and CA9 targets to disrupt oncogenic signaling.
Conclusions:
FZKAF orchestrates apoptosis induction and growth suppression in HCC, at least partially, by modulating the KLF4/HIF-1a/CA9 signaling axis, revealing a novel druggable pathway that advances precision oncology strategies for HCC patients.
Clinical studies have established the efficacy of Fuzheng Kang’ai formula (FZKAF) in hepatocellular carcinoma (HCC) management. The molecular basis of FZKAF’s HCC-suppressive effects is not fully characterized. This investigation aimed to mechanistically delineate FZKAF’s therapeutic actions against HCC.
Material and methods:
Phytochemical characterization via liquid chromatography-mass spectrometry (LC-MS) established the decoction’s bioactive constituents. CCK-8 assays quantified proliferative suppression and cytotoxicity, while Annexin V-FITC/PI staining and cell cycle analysis mapped apoptosis induction. Integrated proteomic and transcriptomic profiling screened core targets and signaling pathways. Therapeutic efficacy was ultimately confirmed in an orthotopic HCC nude mouse model.
Results:
Phytochemical profiling identified 33 bioactive compounds in serum following FZKAF administration, including 9 established anti-tumor agents such as paeoniflorin, catechin, kaempferol, and quercetin. Functionally, FZKAF demonstrated dual anti-HCC efficacy by suppressing tumor growth in vivo and inhibiting 97H cell proliferation in vitro while promoting apoptosis through mitochondrial dysfunction. Mechanistic interrogation via multi-omics revealed FZKAF coordinately modulates KLF4, HIF-1a, and CA9 targets to disrupt oncogenic signaling.
Conclusions:
FZKAF orchestrates apoptosis induction and growth suppression in HCC, at least partially, by modulating the KLF4/HIF-1a/CA9 signaling axis, revealing a novel druggable pathway that advances precision oncology strategies for HCC patients.
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| ISSN: | 1734-1922 |
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