啮齿类动物常位脑瘤异种移植中的腹膜内雷帕霉素和纳米脂质体CPT-11对流增强输送的联合治疗

Title:Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts

Volume: 15 Issue: 4

Author(s): Marina Mendiburu-Elicabe and Jon Gil-Ranedo

Affiliation:

关键词: 联合，CPT-11，神经胶质瘤，雷帕霉素，疗法。

摘要: Background: Glioblastoma multiforme (GBM) is the most malignant histological type of glioma. It exhibits an extremely aggressive action including invasion of large zones of brain parenchyma. Even after the application of surgery, radio and chemotherapy, the effect and survival for patients with GBM continue to be very poor. The PI3K/AKT/mTOR is a key pathway in the regulation of the proliferation of cancer cells. This is the reason to consider the mTOR inhibitors such as rapamycin analogs as an encouraging therapy for malignant glioma, but current investigations suggest that single inhibition of mTOR may be insufficient. For this reason, there is a need for the use of more than one agent rationally combined.

Methods: In this study, we have evaluated the therapeutic potential of the combination of two different drugs: intraperitoneal rapamycin and convection enhanced delivery of nanoliposomes containing the topoisomerase I inhibitor CPT-11. The effect was analyzed by flow cytometry, cell growth, immunocytochemistry and immunohistochemistry, and rodent orthotopic xenograft survival analysis.

Results: The combination presented remarkable efficacy in a survival study. We present an increase in survival of 6-fold in xenotransplanted animals without rise in toxicity.

Conclusion: In summary, we propose a very powerful new combination therapy for glioma.

Cite this article as:

Marina Mendiburu-Elicabe and Jon Gil-Ranedo , Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts, Current Cancer Drug Targets 2015; 15 (4) . https://dx.doi.org/10.2174/1568009615666150225123120