Proinflammatory effects of photoactivated methylene blue on rat model of Walker 256 carcinosarcoma

Abstract

Photodynamic therapy (PDT) is an anticancer therapy that associates the photosensitizer (PS), oxygen and light to destroy cancer cells. Methylene blue (MB) is considered a second generation phenothiazine dye with excellent photochemical properties. Aim: To evaluate whether MB-mediated PDT can induce oxidative stress and inflammation, therefore, interfering tumor growth. Materials and Methods: The study was conducted on Wistar rats transplanted with Walker 256 carcinosarcoma (W256). The proinflammatory interleukins levels (IL-1ß, IL-6, IL-10, TNF-a) were determined by ELISA, mRNA expression of COX-1, COX-2, iNOS and eNOS by RT-PCR, lipid peroxidation was measured by the TBARS method. Moreover, myeloperoxidase (MPO) activity in neutrophils was determined by MPO activity assay. All indices mentioned above were determined in tumor tissue. Kaplan — Meier and Gehan — Breslow — Wilcoxon tests were used for survival analysis. Results: We found that the treatment of W256 with 0.1% MB + 1 J/cm2 provoked a significant increase in the interleukins levels (IL-1ß, IL-6, IL-10, TNF-a), prostaglandin E2, the mRNA expression of COX-2, iNOS, lipid peroxidation and MPO activity in tumor tissue, which were statistically different (p < 0.05) compared to other experimental and control groups. The results of the estimation of survival curves show a greater probability of survival in 0.1% MB + 1 J/cm2 (total energy dose =142.8 J/cm2 ) treated group. Conclusion: Our results suggest that treatment of W256 with 0.1% MB + 1 J/cm2 was able to promote cytotoxic effects in tumor tissue by the generation of reactive oxygen species causing inflammation and thus interfering in the tumor growth