Inhibition of Gemcitabine-Induced Autophagy in Cancer-Associated Fibroblasts Reduces Collagen I and Enhances Chemotherapeutic Efficacy in Pancreatic Cancer.
Song D., Tang H., You T., Ying J., Bai C., Sun Z.
Animal Study, published in Stem Cells Dev (2026) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Stem Cells Dev (2026)
- Country
- United States
- Reported sample size
- —
- Source database
- PubMed
- PMID
- 41981800
- DOI
- 10.1177/15473287261442512
Abstract (original English)
In pancreatic cancer, increased collagen I impairs the efficacy of gemcitabine; however, the role of gemcitabine itself in collagen I accumulation remains unclear. This study aims to explore the mechanism of gemcitabine-induced fibrosis and provide new insights to enhance its therapeutic efficacy. We analyzed COL1A1 expression in pancreatic cancer patient tumor tissues and found that gemcitabine treatment upregulated COL1A1 expression. Subsequently, cancer-associated fibroblasts (CAFs) were modeled by inducing human adipose-derived mesenchymal stem cells with tumor-derived exosomes. Using the autophagy inhibitor chloroquine (CQ) and the protein kinase B (AKT) activator SC79, we demonstrated that gemcitabine downregulated P62 expression and upregulated LC3BII, Beclin-1 expression, inducing autophagy in CAFs via decreasing AKT phosphorylation, which further led to collagen I accumulation. In addition, gemcitabine combined with CQ enhanced cell death in both CAFs and tumor cells, while inhibiting tumor cell proliferation and migration. In animal models, this combination therapy reduced gemcitabine-induced autophagy and collagen I deposition, contributing to delayed tumor growth. Collectively, gemcitabine upregulates collagen I by inducing CAF autophagy via reducing AKT phosphorylation. Targeting CAF autophagy can reduce collagen deposition, offering a promising strategy to improve
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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