Ciência e terapia do câncer

Combined use of Anti-VEGF and Anti-EGFR Monoclonal Antibodies with Photodynamic Therapy Suppresses Tumor Growth in an In vivo Tumor Model

Abstract

Ramaswamy Bhuvaneswari, Patricia Thong, Gan Yik Yuen, Malini Olivo and Soo Khee Chee

Photodynamic therapy (PDT) is a promising treatment option for cancer. It can be used for drug-resistant and
inoperable tumors. However, one of the unsolved problems in PDT is tumor recurrence. The aim of this study is to
suppress tumor regrowth by including angiogenesis inhibitors that target vascular endothelial growth factor (VEGF)
and epidermal growth factor receptor (EGFR) pathways, to the PDT protocol. Human bladder cancer (MGH cell
line) xenografts were induced in Balb/c nude mice. The animals treated with PDT received an intravenous injection
of hypericin followed by irradiation after 6 hours, with a broadband light source through a 560-640 NM bandpass
filter. A light dosage of 120 J/cm2 and 100 mW/cm2 was administered. Angiogenesis inhibitors, bevacizumab
and cetuximab were administered at a dose of 10 mg/kg. Treatment efficacy was assessed by monitoring the
tumor growth inhibition of xenograft tumors. Immunohistochemistry was performed to evaluate the expression
of VEGF and EGFR. Expression of the major proteins in the VEGF and EGFR pathways was investigated by
immunoblotting. One-way ANOVA with Bonferroni correction was performed to analyze the data. Tumors treated
with the combination of PDT and inhibitors exhibited significantly greater treatment response compared to control
and PDT groups. Downregulation of VEGF and EGFR observed in tumors treated with PDT + bevacizumab
and cetuximab respectively. Our results show that blocking VEGF or/and EGFR pathways along with PDT can
effectively suppress tumor growth.