Seidkhani Elham, Moradi Fatemeh, Rustamzadeh Auob, Simorgh Sara, Shirvalilou Sakine, Mehdizadeh Mehdi, Dehghani Hamed, Akbarnejad Zeinab, Motevalian Manijeh, Gorgich Enam Alhagh Charkhat
Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Toxicol Appl Pharmacol. 2023 Dec 15;481:116754. doi: 10.1016/j.taap.2023.116754. Epub 2023 Nov 11.
Glioblastoma multiforme (GBM) is one of the most vascular among solid tumors, and despite the use of multimodal therapies, the survival of these patients is poor. In order to target angiogenesis in GBM as a promising strategy, an antiangiogenic drug is required. This study was designed to evaluate the effects of sunitinib, a multityrosine kinase inhibitor with tumor proliferation and angiogenesis inhibitory properties, on GBM-bearing rats. Given the ineffective drug delivery to the brain due to the presence of the blood-brain barrier (BBB), intra-nasal (IN) drug delivery has recently been considered as a non-invasive method to bypass BBB. Therefore, in the current study, IN was used as an ideal method for the delivery of sunitinib to the brain, and the effects of this method were also compared to the OR administration of the sunitinib. GBM was induced in the brain of male Wistar rats, and they were randomly divided into 4 groups; IN-STB (sunitinib intranasal delivery), IN-sham (placebo intranasal delivery), OR-STB (sunitinib oral delivery) and OR-sham (placebo oral delivery). After the end of the treatment period, an MRI of animals' brains showed a reduction in tumor growth in the treatment groups. Immunohistochemistry revealed that sunitinib inhibits angiogenesis in GBM in both OR and IN delivery methods. Analysis of liver tissue and enzymes showed that IN delivery of sunitinib had less hepatotoxicity than the OR method. Overall, it was found that IN sunitinib delivery could be used as a potential non-hepatotoxic alternative for the treatment of GBM.
多形性胶质母细胞瘤（GBM）是实体瘤中血管最为丰富的肿瘤之一，尽管采用了多模式治疗方法，但这些患者的生存率仍然很低。为了将靶向GBM血管生成作为一种有前景的策略，需要一种抗血管生成药物。本研究旨在评估舒尼替尼（一种具有肿瘤增殖和血管生成抑制特性的多酪氨酸激酶抑制剂）对荷GBM大鼠的影响。鉴于血脑屏障（BBB）的存在导致药物难以有效递送至脑内，鼻内（IN）给药最近被认为是一种绕过BBB的非侵入性方法。因此，在本研究中，IN被用作将舒尼替尼递送至脑内的理想方法，并且还将该方法的效果与舒尼替尼的口服给药进行了比较。在雄性Wistar大鼠脑内诱导GBM，然后将它们随机分为4组；IN-STB（舒尼替尼鼻内给药）、IN-假手术组（安慰剂鼻内给药）、OR-STB（舒尼替尼口服给药）和OR-假手术组（安慰剂口服给药）。治疗期结束后，对动物脑部进行的MRI显示治疗组的肿瘤生长有所减少。免疫组织化学显示，舒尼替尼在口服和鼻内给药方式下均能抑制GBM中的血管生成。肝脏组织和酶分析表明，舒尼替尼的鼻内给药比口服方法具有更低的肝毒性。总体而言，发现鼻内给予舒尼替尼可作为治疗GBM的一种潜在的无肝毒性替代方法。
