The effects of Photofrin-mediated photodynamic therapy on the modulation of EGFR in esophageal squamous cell carcinoma cells

Abstract

Photodynamic therapy (PDT) has been demonstrated to be an effective minimally invasive treatment modality for early esophageal cancer. However, the molecular action in esophageal cancer during PDT is hardly known. EGFR has been known to downregulate in various cancer cells during PDT. In this study, we investigated the effects of Photofrin-mediated PDT on cell death and expression of EGFR in CE48T/VGH (CE48T) esophageal squamous cell carcinoma cells. We found that the photosensitizer Photofrin in the absence of light exposure can downregulate the expression of EGFR at both transcription and translation levels. Higher concentrations of Photofrin results in cytotoxicity whereas lower doses of Photofrin inhibit EGFR expression under dark control without inducing significant cell death. This Photofrin-associated inhibition of EGFR was repeated in lung cancer, cervical cancer, and glioblastoma cells. Another esophageal squamous cell carcinoma cell line CE81T/VGH (CE81T) was found to be resistant to Photofrin-induced inhibition of EGFR as well as to Photofrin-mediated dark toxicity compared with CE48T. The resistance to the cytotoxicity in CE81T cells became insignificant when the Photofrin-treated cells were further irradiated by red light (Photofrin-PDT). We suggest Photofrin modulates the expression of EGFR in cancer cells. However, efficient cell death still requires the combination of Photofrin and light irradiation in esophageal squamous cell carcinoma cells.

The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells

“…Complementary DNA (cDNA) was generated from the RNA by reverse transcription (RT) following the manufacturer's instructions (Promega). Quantitative PCR (Q-PCR) was then performed on the cDNA with SYBR Green I fluorescence using SYBR Green/Fluorescein qPCR Master Mix (Fermentas), and the results were analyzed by iQ5 RealTime PCR Detection System (Bio-Rad) as described previously [32]. The primer pair for detecting TNF messenger RNA (mRNA) was 5′-ATG AGC ACA GAA AGC ATG ATC-3′ (forward) and 5′-TAC AGG CTTGTC ACT CGGGGT-3′ (reverse) [33].…”

“…The in vitro Photofrin-PDT treatment was performed mostly as previously described [32]. For the survival assay, the cells were plated in a 96-well plate at 8×10 3 cells/well.…”

Pleural Photodynamic Therapy and Surgery in Thoracic Cancer Patients with Pleural Spread

“…However, the PDT is only one of the multi-modality treatments, so the adjuvant or neoadjuvant therapy is important, too. Our group conducted another experiment about the signiicance of the Epidermal Growth Factor Receptor (EGFR) proile to the PDT-sensitive cancer cells [21]. Because tyrosine kinase inhibitor (TKI) was popularly used in the advanced lung cancer, we investigated the roles of this two common therapies combined.…”

Tumor Microenvironment as a Determinant of Photodynamic Therapy Resistance

“…Several reports have highlighted "resistance" to PDT as a result of treatmentinduced changes to tumor and endothelial cell biology [68,69]. The most common molecules known to impair PDT response due to alteration in their expression or signaling following light treatment include the epidermal growth factor receptor (EGFR) [70][71][72], ERKs [73,74], signal transducer and activator of transcription 3 (STAT3) [70], cyclooxygenase 2 (COX-2) [75,76], heat shock proteins (Hsp) [67,68,77], matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) [78][79][80]. These proteins contribute to tumor progression through processes that include the induction of survival signaling, cell growth and proliferation, promotion of cell motility and metastasis, inflammation, angiogenesis, and prevention of apoptosis.…”