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Войти в исследования Anticancer research · 2025
High Antitumor Effects and Reduced Side Effects of Doxorubicin Prodrug Active Only Under Hypoxic Conditions.
СтатьяНазвание и аннотация: Перевод в очереди
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Yoshioka Koki, Furuta Taisuke, Sakuda Tomohiko, Oda Akihiro, Ikeda Yutaka, Miyaki Shigeru, Nagasaki Yukio, Adachi Nobuo
Аннотация
BACKGROUND/AIM: Doxorubicin (DOX) is the most impactful drug developed for osteosarcoma. However, despite its therapeutic effects, it also causes serious side effects, such as cardiotoxicity and hemotoxicity. To address this, we developed a novel DOX prodrug that exhibits high antitumor activity specifically in hypoxic regions while demonstrating low toxicity in normal organs. Based on these properties, we evaluated its efficacy against osteosarcoma with the aim of significantly reducing side effects while maintaining therapeutic efficacy.
MATERIALS AND METHODS: To evaluate antitumor effects, tumor diameter changes were measured in osteosarcoma cell line-bearing mice divided into the following groups: control, DOX 8 mg/kg, DOX prodrug 8 mg/kg, and 5 doses of DOX prodrug 16 mg/kg every other day. To evaluate side effects, blood samples were collected 2 weeks after treatment in all groups to determine the complete blood count and aspartate aminotransferase, alanine aminotransferase, creatinine, and blood urea nitrogen levels. After the mice were sacrificed, sections of the liver, kidney, heart, and testes were prepared for histological evaluation.
RESULTS: Regarding antitumor effects, the DOX and DOX prodrug groups showed comparable reductions in tumor size when compared to the control group. Blood test results showed that mice in the DOX prodrug group had no leukopenia or liver dysfunction. Histological evaluation revealed that the DOX prodrug group showed significantly less myocardial damage and gonadal toxicity compared to the DOX group.
CONCLUSION: The DOX prodrug developed by our group showed tumor-suppressive effects comparable to those of DOX while being able to suppress blood toxicity, cardiotoxicity, as well as liver and testicular dysfunction.
MATERIALS AND METHODS: To evaluate antitumor effects, tumor diameter changes were measured in osteosarcoma cell line-bearing mice divided into the following groups: control, DOX 8 mg/kg, DOX prodrug 8 mg/kg, and 5 doses of DOX prodrug 16 mg/kg every other day. To evaluate side effects, blood samples were collected 2 weeks after treatment in all groups to determine the complete blood count and aspartate aminotransferase, alanine aminotransferase, creatinine, and blood urea nitrogen levels. After the mice were sacrificed, sections of the liver, kidney, heart, and testes were prepared for histological evaluation.
RESULTS: Regarding antitumor effects, the DOX and DOX prodrug groups showed comparable reductions in tumor size when compared to the control group. Blood test results showed that mice in the DOX prodrug group had no leukopenia or liver dysfunction. Histological evaluation revealed that the DOX prodrug group showed significantly less myocardial damage and gonadal toxicity compared to the DOX group.
CONCLUSION: The DOX prodrug developed by our group showed tumor-suppressive effects comparable to those of DOX while being able to suppress blood toxicity, cardiotoxicity, as well as liver and testicular dysfunction.