Tanshinone IIA Inhibits Epithelial-Mesenchymal Transition in Colitis-Associated Cancer in Mice by Regulating PTEN and ATPase Inhibitory Factor 1.

INTRODUCTION

Chronic inflammation in patients with inflammatory bowel disease (IBD) significantly increases the risk of developing gastrointestinal malignancies. Although Tanshinone IIA (TanIIA) has demonstrated biological activity against IBD, its specific effects on colitis-associated cancer (CAC) remain poorly understood. This study aimed to elucidate the therapeutic impact of TanIIA in CAC and to investigate its underlying molecular mechanisms.

METHODS

A murine model of CAC was established using azoxymethane (AOM) and dextran sulfate sodium (DSS). Phenotypic measurements were recorded, and colon pathology was assessed using hematoxylin and eosin (H&E) staining. Quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were performed to examine the expression of colonic phosphatase and tensin homolog (PTEN), interleukin-17 (IL-17), NAD(P)H quinone oxidoreductase 1 (NQO1), E-cadherin, and N-cadherin.

RESULTS

TanIIA modulated the PTEN/IL-17 axis to reduce tumor burden at week 10. By week 13, however, TanIIA did not reduce tumor size due to NQO1-mediated reactive oxygen species (ROS) generation, which influenced ATPase inhibitory factor 1 (IF1) expression in colon tissues and subsequently reversed epithelial-mesenchymal transition (EMT).

DISCUSSION: While TanIIA failed to decrease late-stage tumor size, it effectively inhibited tumor initiation via the PTEN/IL-17 axis and suppressed metastatic potential through ROS-triggered IF1 upregulation. The absence of in vitro and clinical validation, however, necessitates further studies before clinical application.

CONCLUSION

TanIIA limits CAC progression in vivo by modulating early-stage tumor initiation through the PTEN/IL-17 axis and late-stage EMT via ROS-mediated IF1 regulation, highlighting its potential as a therapeutic candidate for CAC and anti-metastatic treatment.