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Role of NF‐κB/Snail/RKIP loop in the response of tumor cells to photodynamic therapy
Author(s) -
Rapozzi Valentina,
Umezawa Kazuo,
Xodo Luigi E.
Publication year - 2011
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.21095
Subject(s) - snail , photodynamic therapy , apoptosis , nf κb , western blot , cancer research , photosensitizer , chemistry , cell , melanoma , blot , microbiology and biotechnology , biology , biochemistry , ecology , organic chemistry , gene
Background and Objective Photodynamic therapy (PDT) is a therapeutic modality whose efficacy depends on several factors including type of photosensitizer, light fluence and cellular response. Cell recurrence is one of the problems still unsolved in PDT. In this work we found that in B78‐H1 murine amelanotic melanoma cells there is a correlation between cell recurrence and the NF‐κB/Snail/RKIP loop. Materials and Methods Proliferation and migration of surviving cells were analyzed by MTT and wound‐scratch assays. The levels of ROS/NO in B78‐H1 melanoma cells treated with pheophorbide a (Pb a ) and light (Pb a /PDT) were measured by FACS, while expression of NF‐κB, Snail and RKIP were determined by Western blots. The mechanism of cell death was investigated by caspase and microscopy assays. Results Our data show that after a low‐dose Pb a /PDT treatment, B78‐H1 cells are able to recover. This correlates with a low level of NO production, which blocks apoptosis via NF‐κB pathway. Western blot analyses showed that a low‐dose Pb a /PDT increases the expression of NF‐κB and anti‐apoptotic Snail, but reduces the expression of pro‐apoptotic RKIP. The role played by NF‐κB in the modulation of Snail and RKIP was investigated using DHMEQ: a NF‐κB inhibitor which behaves as NO donor. DHMEQ caused a decrease of Snail and an increase of RKIP expression. When B78‐H1 cells were treated with a low dose Pb a /PDT and DHMEQ, the NO level strongly increased, with the result that Snail was down‐regulated and RKIP was upregulated, as observed with a high‐dose Pb a /PDT. Conclusion One major problem in PDT is the cellular rescue occurring in tissue regions receiving a low‐dose PDT. To minimize this problem and sensitize cancer cells to PDT we propose a combined treatment in which the photosensitizer is delivered with a donor of NO acting on the NF‐κB/Snail/RKIP loop. Lasers Surg. Med. 43:575–585, 2011. © 2011 Wiley‐Liss, Inc.