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

Background: 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-1β, IL-6, IL-10, TNF-α) 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/cm provoked a significant increase in the interleukins levels (IL-1β, IL-6, IL-10, TNF-α), 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/cm (total energy dose =142.8 J/cm) treated group.

Conclusion: Our results suggest that treatment of W256 with 0.1% MB + 1 J/cm 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.