Proinflammatory effects of photoactivated methylene blue on rat model of Walker 256 carcinosarcoma.
Proinflammatory effects of photoactivated methylene blue on rat model of Walker 256 carcinosarcoma.
复制标题
光活化亚甲蓝对 Walker 256 癌肉瘤大鼠模型的促炎作用。
DOI：
10.32471/exp-oncology.2312-8852.vol-41-no-2.13047
复制
发表时间：
2019
影响因子：
--
通讯作者：
R. Lopes
中科院分区：
文献类型：
--
作者：
M. Petrellis;L. Frigo;W. Ribeiro;E. C. Leal;F. Oliveira;D. Maria;R. Lopes
背景
光动力疗法（PDT）是一种结合光敏剂（PS）、氧气和光来破坏癌细胞的抗癌疗法。亚甲蓝（MB）被认为是具有优异光化学性能的第二代吩噻嗪染料。
目的
评估MB介导的PDT是否可以诱导氧化应激和炎症，从而干扰肿瘤生长。
材料和方法
该研究是在移植了 Walker 256 癌肉瘤 (W256) 的 Wistar 大鼠上进行的。通过ELISA测定促炎白细胞介素水平（IL-1β、IL-6、IL-10、TNF-α），通过RT-PCR测定COX-1、COX-2、iNOS和eNOS的mRNA表达，通过TBARS方法测定脂质过氧化。此外，通过MPO活性测定测定中性粒细胞中的髓过氧化物酶(MPO)活性。上述所有指标均在肿瘤组织中测定。 Kaplan - Meier 和 Gehan - Breslow - Wilcoxon 检验用于生存分析。
结果
我们发现，用 0.1% MB + 1 J/cm2 治疗 W256 引起肿瘤组织中白细胞介素水平（IL-1β、IL-6、IL-10、TNF-α）、前列腺素 E2、COX-2、iNOS、脂质过氧化和 MPO 活性的显着升高，与其他实验组和对照组相比具有统计学差异（p < 0.05）。生存曲线估计结果显示，0.1% MB + 1 J/cm2（总能量剂量=142.8 J/cm2）治疗组的生存概率更大。
结论
我们的结果表明，用 0.1% MB + 1 J/cm2 处理 W256 能够通过产生引起炎症的活性氧来促进肿瘤组织中的细胞毒性作用，从而干扰肿瘤生长。
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/cm2 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/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.