Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy

Abstract

Background: Glioblastoma (GBM) is the most common and deadly type of brain cancer in adults. Dysregulation of receptor tyrosine kinase pathways, such as the epidermal growth factor receptor (EGFR), contributes to therapeutic resistance. Drugs that inhibit tyrosine kinase activity and monoclonal antibodies against EGFR are strategies used in clinical trials. Photodynamic therapy (PDT) is a tumor treatment that involves the administration of a photosensitizing drug, followed by its activation with visible light, which causes cell death due to oxidative stress. Although PDT helps prolong median survival in patients with GBM, complete remission has not been achieved. Populations of GBM cells have been obtained from the T98G line resistant to PDT with methyl-5-aminolevulinic acid (Me-ALA) for characterization, comparing them with the original parental population. Objective: The objective of this work was to evaluate the general response of T98G GBM cells resistant to PDT when EGFR activity is inhibited with the drug erlotinib. Methods and Results: It has been observed that the administration of the EGFR inhibitor drug in combination with PDT reduced viability (MTT) in resistant populations compared to PDT alone. Furthermore, the PpIX content (flow cytometry) was increased in the resistant population when cells were incubated with Me-ALA and erlotinib. Erlotinib prevented cell proliferation of parental and resistant spheroids. Wound closure was reduced in both parental and PDT-resistant populations. Conclusions: Our results indicate that EGFR activation would be relevant in the resistance of GBM cells to PDT.