2. Academic Validation
  3. "Huanglianjiedu Decoction" Against Pancreatic Adenocarcinoma Proliferation of by Downregulating the PI3K/AKT/mTOR and MAPK/ERK1/2 Signaling Pathways

"Huanglianjiedu Decoction" Against Pancreatic Adenocarcinoma Proliferation of by Downregulating the PI3K/AKT/mTOR and MAPK/ERK1/2 Signaling Pathways

  • J Evid Based Integr Med. 2024 Jan-Dec:29:2515690X241291381. doi: 10.1177/2515690X241291381.
Shu Dong Md 1 2,  Panling Xu Md 1 3,  Peiwen Yang Md 1 2,  Juying Jiao Md 1 2,  Chien-Shan Cheng Md PhD 1 2 4,  Lianyu Chen Md PhD 1 2
Affiliations

Affiliations

  • 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 3 Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • 4 Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.
PMID: 39410848 DOI: 10.1177/2515690X241291381
Abstract

Background: Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear.

Aims: This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways.

Methods: A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays.

Results: HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced Apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were Cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2.

Conclusion: HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/Akt/mTOR and MAPK/ERK1/2 signaling pathways.

Keywords

HLJDD; network pharmacology; pancreatic ductal adenocarcinoma; traditional Chinese medicine; tumor microenvironment.

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