Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 16, Issue 8, Pages 19960-19977Publisher
MDPI
DOI: 10.3390/ijms160819960
Keywords
phototherapy; inflammation; anti-tumor immunity; siRNA; interleukin-6; tumor necrosis factor alpha; monocyte chemotactic protein 1 interleukin-10; interleukin-12p70; interferon gamma
Funding
- Dutch Anti-Cancer Society (Stichting Nationaal Fonds Tegen Kanker, Amsterdam, The Netherlands)
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Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor B (NF-B) has been identified as a potential pharmacological target, albeit inhibition of NF-B may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects. In contrast to these postulations, this study demonstrated that siRNA knockdown of NF-B in murine breast carcinoma (EMT-6) cells increased survival signaling in these cells and exacerbated the inflammatory response in murine RAW 264.7 macrophages. These results suggest a pro-death and immunosuppressive role of NF-B in PDT-treated cells that concurs with a hyperstimulated immune response in innate immune cells.
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