mTHPC‐mediated Photodynamic Treatment Up‐regulates the Cytokines VEGF and IL‐1alpha

Abstract

Photodynamic therapy (PDT) of cancer induces oxidative stress, which intervenes in the expression of cytokines by tumor cells. The cytokines might have either a positive or a negative impact on tumor eradication. Here, we studied the expression of cytokines vascular endothelial growth factor (VEGF) and interleukin-1alpha (IL-1alpha) in the human epidermoid carcinoma A-431 cells following m-tetra(3-hydroxyphenyl)-chlorin (mTHPC)-mediated PDT in vitro and assessed the IL-1alpha effect on VEGF expression. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay revealed the enhanced production of VEGF and IL-1alpha both on mRNA and protein levels by mTHPC-loaded cells after light exposure. The silencing of IL1A by small interfering RNA resulted in decreased production of IL-1alpha and a reduced amount of VEGF. Furthermore, exogenous recombinant IL-1alpha stimulated the VEGF expression after PDT. Thus, in addition to the cytotoxic action on the A-431 cells, mTHPC-mediated PDT stimulated the production of VEGF and IL-1alpha, and IL-1alpha contributed to the VEGF overexpression. These data establish IL-1alpha as a possible target of combined cancer treatment.

The Use of Fractal Dimension Analysis in Estimation of Blood Vessels Shape in Transplantable Mammary Adenocarcinoma in Wistar Rats after Photodynamic Therapy Combined with Cysteine Protease Inhibitors

“…The general increase of blood vessel number in PDT+CPI group may suggest intensification of angiogenesis. Angiogenesis may be a result of the feedback as a response to destruction of blood vessels during PDT and to the increase in secretion of VEGF and bFGF [3–5]. The increase of vessel number next to reduction of fractal dimension proves that diameter of vessels decreases (the lower fractal dimension—near to 0—the shape more similar to point which may be interpreted as a reduction of diameter).…”

“…Immunohistochemical staining is very useful against specific proteins within blood vessel wall, for example vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), cluster of differentiation such as CD34, and others [1, 2]. Many studies show that PDT is responsible for overexpression of VEGF in vivo and in vitro [3–5]. However, in the case of such complex and chaotic shapes of tumor blood vessels classic methods of evaluation may fail.…”

Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer

“…Interleukin-1 alpha is a pro-inflammatory cytokine that is involved in angiogenesis and metastasis. ILIA can directly stimulate the synthesis of VEGF ( 69 ) and fibroblastic pro matrix metallic proteinase I ( 70 , 71 ). IL1A causes resistance to EGFR inhibitors in both colon and head and neck cancers ( 72 , 73 ).…”

The Role of Interleukin-1 in Inflammatory and Malignant Human Skin Diseases and the Rationale for Targeting Interleukin-1 Alpha

“…Dabkevicien et al used IL-1α to stimulate vascular endothelial growth factor (VEGF) expressions in A-431 epidermoid carcinoma cells after photodynamic therapy (PDT). 74 Another study on liver metastasis from human gastric cell lines showed similar activity of IL-1α in angiogenesis and metastasis through the stimulation of fibroblastic pro-matrix metalloproteinase 1 (pro-MMP1) synthesis. 75,76 2.…”

“…• Inflammation initiation and maintenance 9,15,[67][68][69][70] • Activation of the IL-1RI [38][39][40] • Carcinogenesis [74][75][76] • Alteration of tight junctions 84,85 • Systemic extracellular function 23 • Acute and chronic inflammation 9,15 • Activation of the IL-1RI [38][39][40] • Carcinogenesis 66,86,92 proIL-1, pro-interleukin-1; IL-1, interleukin-1; IL-1R, interleukin-1 receptor. The release proIL-1␤ is inactive.…”