在携带实体艾氏癌的小鼠中，游离或负载纳米颗粒（有无阿霉素）的卡维地洛的潜在心脏保护和抗癌作用。
Potential cardioprotective and anticancer effects of carvedilol either free or as loaded nanoparticles with or without doxorubicin in solid Ehrlich carcinoma-bearing mice.
作者信息
Zidan Amr, El Saadany Amira A, El Maghraby Gamal M, Abdin Amany A, Hedya Sabeha E
机构信息
Department of Pharmacology, Faculty of Medicine, Tanta University, Egypt.
Department of Pharmacology, Faculty of Medicine, Tanta University, Egypt.
出版信息
Toxicol Appl Pharmacol. 2023 Apr 15;465:116448. doi: 10.1016/j.taap.2023.116448. Epub 2023 Mar 13.
AIM
The aim of this study was to investigate the potential cardioprotective and anti-cancer effects of carvedilol (CAR) either free or as loaded nano-formulated with or without doxorubicin (DOX) in solid Ehrlich carcinoma (SEC)-bearing mice. It focused on assessment of cardiac damage, drug resistance, apoptosis, oxidative stress status, angiogenesis and proliferation.
METHODS
CAR was loaded into poly-D,L lactic-co-glycolic acid)PLGA(or Niosomes. SEC was induced in female albino mice as an experimental model of breast cancer. Seventy-two mice were randomly divided into 9 equal groups (Normal control, Untreated-SEC, SEC + DOX, SEC + CAR-free, SEC + CAR-PLGA, SEC + CAR-Niosomes, SEC + DOX + CAR-free, SEC + DOX + CAR-PLGA and SEC + DOX + CAR-Niosomes). Tumor volume and survival rate were recorded. On day 28 from tumor inoculation, mice were sacrificed, and blood samples were collected for determination of serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB). One part from tumor tissues was prepared for assessment of multidrug resistance protein-1 (MDR-1), caspase-3, reduced glutathione (GSH) and malondialdehyde (MDA), while the other part was processed for histopathological examination and immunohistochemical expression of vascular endothelial growth factor (VEGF) and Ki-67.
RESULTS
There was non-significant difference between CAR-free, CAR-PLGA and CAR-Niosomes as anticancer either alone or when combined with DOX. However, CAR-free demonstrated potential cardioprotective effects against cardiac damage mediated by cancer or DOX that have been enhanced using CAR-PLGA or CAR-Niosomes, but that of Niosomes outperformed them both.
CONCLUSION
CAR could be used as an adjuvant therapy with DOX, especially when nanoformualted with PLGA and even better with Niosomes, without compromising its cytotoxicity against cancer cells and preventing its cardiotoxic impacts.
目的
本研究旨在探究卡维地洛（CAR）游离形式或与阿霉素（DOX）一起制成纳米制剂（有或无DOX）对荷实体艾氏癌（SEC）小鼠的潜在心脏保护和抗癌作用。研究重点在于评估心脏损伤、耐药性、细胞凋亡、氧化应激状态、血管生成和增殖情况。
方法
将CAR载入聚-D,L-乳酸-乙醇酸共聚物（PLGA）或脂质体中。在雌性白化病小鼠中诱导产生SEC作为乳腺癌实验模型。72只小鼠随机分为9个相等的组（正常对照组、未治疗的SEC组、SEC + DOX组、SEC + 游离CAR组、SEC + CAR-PLGA组、SEC + CAR-脂质体组、SEC + DOX + 游离CAR组、SEC + DOX + CAR-PLGA组和SEC + DOX + CAR-脂质体组）。记录肿瘤体积和存活率。在接种肿瘤后第28天，处死小鼠，采集血样以测定血清乳酸脱氢酶（LDH）和肌酸激酶同工酶MB（CK-MB）。取一部分肿瘤组织用于评估多药耐药蛋白-1（MDR-1）、半胱天冬酶-3、还原型谷胱甘肽（GSH）和丙二醛（MDA），另一部分用于组织病理学检查以及血管内皮生长因子（VEGF）和Ki-67的免疫组化表达检测。
结果
游离CAR、CAR-PLGA和CAR-脂质体单独或与DOX联合使用时，作为抗癌药物，它们之间无显著差异。然而，游离CAR对癌症或DOX介导的心脏损伤具有潜在的心脏保护作用，使用CAR-PLGA或CAR-脂质体可增强这种作用，但脂质体的效果优于二者。
结论
CAR可与DOX联合用作辅助治疗，尤其是当与PLGA制成纳米制剂时，与脂质体制成纳米制剂效果更佳，且不影响其对癌细胞的细胞毒性，并能防止其心脏毒性作用。
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