Abstract

Melanoma is the deadliest type of skin cancer. Treatments that directly address tumor survival are required. Indomethacin (IND) is a well-known drug used worldwide. Although widely used as a therapeutic agent, IND has undesirable gastrointestinal effects.

Purpose

To investigate the antitumor efficacy of IND incorporated into mesoporous silica nanoparticles (MSNPs+IND), as well as its toxic potential in a syngeneic murine B16 melanoma model.

Methods

Antitumor activity was evaluated by measuring tumor size and weight and by histopathological analysis. Possible molecular signaling pathways involved in the antitumor activity were analyzed by Western blot in liver tissue and by immunohistochemistry in tumor tissue. The potential toxicity was evaluated by determining body and organ weights and by biochemical and genotoxic analysis.

Results

MSNPs+IND treatments inhibited tumor growth by up to 70.09% and decreased the frequency of mitosis in tumor tissues, which was up to 37.95% lower compared to the IND groups. In hepatic tissue, COX-2 levels decreased significantly after treatment with MSNPs+IND and IND. Additionally, MSNPs+IND and IND increased the levels of cleaved caspase-3 (156.25% and 137.50%, respectively), inducing tumor cell apoptosis. Genotoxicity was limited to the group treated with the higher concentration of IND, while MSNPs prevented IND-induced genotoxicity.

Conclusions

MSNPs may be promising for future applications in cancer therapy.

中文翻译：

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吲哚美辛掺入中孔二氧化硅纳米颗粒的抗黑素瘤活性。

摘要

黑色素瘤是最致命的皮肤癌类型。需要直接解决肿瘤生存的治疗方法。消炎痛（IND）是世界范围内使用的知名药物。尽管IND广泛用作治疗剂，但IND具有不希望的胃肠道作用。

目的

研究掺入介孔二氧化硅纳米粒子（MSNPs + IND）中的IND的抗肿瘤功效，及其在同源小鼠B16黑色素瘤模型中的潜在毒性。

方法

通过测量肿瘤的大小和重量以及组织病理学分析来评估抗肿瘤活性。通过肝组织中的蛋白质印迹和肿瘤组织中的免疫组织化学分析了参与抗肿瘤活性的可能的分子信号传导途径。通过确定体重和器官重量以及通过生化和遗传毒性分析来评估潜在的毒性。

结果

MSNPs + IND治疗可抑制肿瘤生长高达70.09％，并降低肿瘤组织中的有丝分裂发生频率，与IND组相比，降低了37.95％。在肝组织中，用MSNPs + IND和IND治疗后，COX-2水平显着下降。此外，MSNPs + IND和IND增加了裂解的caspase-3的水平（分别为156.25％和137.50％），诱导肿瘤细胞凋亡。遗传毒性仅限于用高浓度IND处理的组，而MSNPs可以防止IND诱导的遗传毒性。

结论

MSNP可能在癌症治疗中的未来应用前景广阔。