Combination of photodynamic therapy and temozolomide on glioma in a rat C6 glioma model

• PDT inhibits the expression of P-gp in vivo, circumventing acquired drug resistance.
• PDT increases the concentration of TMZ in glioma tissue in vivo.
• Combining TMZ with PDT enhances the effect of TMZ on glioma cell apoptosis.
• PDT/TMZ combination decreases tumor volume and prolongs survival of rats with glioma.

SummaryBackgroundFor glioma, temozolomide (TMZ) is a commonly used chemotherapy drug and photodynamic therapy (PDT) is an important adjuvant therapy. The aim of this study was to evaluate the effect of their combination for the treatment of glioma.MethodsA rat C6 glioma model using male Wistar rats (n = 180) weighing 280–300 g was established. Glioma-bearing rats (n = 100) were treated with mock, hematoporphyrin monomethyl ether (HMME), laser or PDT. The expression of P-glycoprotein (P-gp) in endothelial cells of the blood–tumor-barrier and in glioma tissues was detected using immunohistochemistry and western blot, respectively. Glioma-bearing rats (n = 40) were treated with normal saline, TMZ (60 mg/m2 for five consecutive days), PDT (630 nm for 10 min) or a combination of TMZ and PDT. TMZ concentration in glioma tissues was detected using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) and cell death was observed using transmission microscopy. Concurrently, another batch of 40 glioma-bearing rats was subjected to the same treatment, and the survival of these rats was estimated using Kaplan–Meier analysis.ResultsPDT significantly decreased the expression of P-gp in endothelial cells comprising the blood–tumor-barrier and in glioma tissues. The combination of TMZ with PDT significantly increased TMZ concentration in glioma tissues, enhanced glioma cell apoptosis and prolonged the median survival of glioma-bearing rats.ConclusionThe combination of PDT with TMZ shows synergistic effect in rat C6 glioma model, indicating its potential clinical use in glioma treatment.