PMID-35935871 – LL-37 Inhibits Pancreatic Cancer via Autophagy Suppression
Zhang Z et al. "LL-37 inhibits pancreatic cancer growth by suppressing autophagy and reprogramming the tumor immune microenvironment," Frontiers in Pharmacology, 2022;13:906625. doi:10.3389/fphar.2022.906625
Quick Reference
| Property | Value |
|---|---|
| PMID | 35935871 |
| DOI | 10.3389/fphar.2022.906625 |
| Year | 2022 |
| Journal | Frontiers in Pharmacology |
| Study Type | Animal in vivo + In vitro |
| Evidence Level | V |
| Sample | Pancreatic cancer cell lines + mouse xenograft models |
| Peptide(s) Studied | LL-37 |
Key Findings
- LL-37 demonstrated significant anti-tumor activity against pancreatic cancer cells both in vitro and in vivo (mouse xenograft models)
- Primary anti-tumor mechanism involves induction of reactive oxygen species (ROS) and DNA damage in cancer cells
- LL-37 suppresses protective autophagy in cancer cells via mTOR pathway activation, preventing the autophagic survival response that typically protects cancer cells from stress
- The peptide reprograms the tumor immune microenvironment by promoting M1 macrophage polarization and increasing CD8+ T cell infiltration
- Combined ROS/DNA damage induction with autophagy suppression creates a synergistic anti-tumor effect — cancer cells cannot activate the protective autophagy response to cope with LL-37-induced oxidative stress
- Tumor growth inhibition was significant in vivo without notable systemic toxicity in mouse models
Study Design
Combined in vitro and in vivo study. In vitro experiments used pancreatic cancer cell lines (PANC-1, BxPC-3) to characterize LL-37 effects on cell viability, ROS production, DNA damage, and autophagy markers. In vivo experiments used subcutaneous xenograft models in nude mice to assess tumor growth inhibition and immune microenvironment changes.
Limitations
- Xenograft models in immunocompromised mice limit assessment of full immune response
- Pancreatic cancer cell line behavior may not fully recapitulate primary tumor biology
- Dose-response relationships and optimal dosing regimens not fully characterized
- No pharmacokinetic data for LL-37 in tumor tissue
- Translation from mouse models to human clinical application remains uncertain
Clinical Relevance
This study identifies a novel anti-tumor mechanism for LL-37 in pancreatic cancer — one of the most lethal malignancies with limited treatment options. The triple mechanism (ROS/DNA damage + autophagy suppression + immune reprogramming) is mechanistically compelling. Importantly, this anti-cancer activity in pancreatic cancer contrasts with the pro-tumorigenic effects of LL-37 reported in some hormone-sensitive cancers, reinforcing the tissue-specific duality of LL-37 in oncology. This supports the growing body of evidence that LL-37 has anti-cancer properties in GI-related cancers.
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#research #animal-in-vivo #evidence-level-V #cancer