Document Type

Article

Publication Date

2026

DOI

10.1007/s10103-026-04825-4

Publication Title

Lasers in Medical Science

Volume

41

Issue

1

Pages

33

Abstract

Cancer-associated fibroblasts (CAFs) within the tumor microenvironment highly contribute to cancer progression and poor prognosis. Recent findings introduce pirfenidone, a medication for pulmonary fibrosis, as a promising repurposed candidate for inhibiting CAFs. Moreover, photobiomodulation (PBM), or low-level laser therapy, has surfaced as a potential modality against cancer; however, its impact on CAFs is not thoroughly comprehended. The present study scrutinized the effects of PBM, pirfenidone, and PBM+pirfenidone on CAFs, and their consequent impact on cancer cells using the CAF-conditioned media. After treating CAFs with PBM at wavelengths 660 and 980 nm with/without PFD and then culturing cancer cells in the prepared conditioned media, cell viability, gene expression, migration, and clonogenic potential were evaluated. Results indicated that PBM reduced the anti-fibrogenic effects of pirfenidone on CAFs and increased their viability. PBM compensated for inhibited migration-inducing effects of CAFs by pirfenidone on cancer cells and promoted their clonogenic potential. Gene expression studies uncovered modulation of EMT and stemness-related genes by PBM and pirfenidone. In conclusion, findings propose that PBM could maintain pro-tumorigenic effects of CAFs even following treatment with the anti-fibrotic agent pirfenidone; therefore, PBM should cautiously be used against cancer before further investigations expound the underlying mechanisms and optimize treatment protocols.

Rights

© The Authors 2026

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if you modified the licensed material. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Data Availability

Article states: "All data generated or analyzed during this study are included in this published article."

Original Publication Citation

Rastegar-Pouyani, N., Nasirpour, A., Javani Jouni, F., Vazini, H., Moshaii, A., & Zafari, J. (2026). Photobiomodulation mitigates the inhibitory effects of pirfenidone on cancer-associated fibroblasts and their pro-tumorigenic properties: A cause for concern. Lasers in Medical Science, 41(1), Article 33. https://doi.org/10.1007/s10103-026-04825-4

ORCID

0000-0001-7614-2775 (Nasirpour)

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