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通过抑制Ki-67和PARP-1利用肿瘤小鼠模型研究菠萝蛋白酶的放射增敏作用

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition.

作者信息

Mekkawy Mai H, Fahmy Hanan A, Nada Ahmed S, Ali Ola S

机构信息

National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Nasr City, Cairo, Egypt.

Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

出版信息

Integr Cancer Ther. 2021 Jan-Dec;20:15347354211060369. doi: 10.1177/15347354211060369.

Abstract

Recent reports have shown that bromelain (BL), a pineapple extract, acts as an adjuvant therapy in cancer treatment and prevention of carcinogenesis. The present study was designed to investigate the possible mechanisms by which BL could radiosensitize tumor cells and in a mouse tumor model. BL has shown a significant reduction in the viability of the radioresistant human breast carcinoma (MCF-7) cell line using cell proliferation assay. The in vivo study was designed using the Ehrlich model in female albino mice, treated with BL (6 mg/kg b. wt., intraperitoneal, once daily for 10 days) 1 hour before exposure to a fractionated dose of gamma radiation (5 Gy, 1 Gy for 5 subsequent days). The radiosensitizing effect of BL was evident in terms of a significant reduction in tumor volume, poly ADP ribose polymerase-1 (PARP-1), the proliferation marker Ki-67 and nuclear factor kappa activated B cells (NF-κB) with a significant elevation in the reactive oxygen species (ROS) content and lipid peroxidation (LPO) in tumor cells. The present findings offer a novel insight into the radiosensitizing effect of BL and its potential application in the radiotherapy course.

摘要

最近的报告显示,菠萝提取物菠萝蛋白酶(BL)在癌症治疗和预防癌变过程中可作为辅助疗法。本研究旨在探讨BL使肿瘤细胞对放疗敏感的可能机制,并在小鼠肿瘤模型中进行研究。使用细胞增殖试验发现,BL可使耐辐射的人乳腺癌(MCF-7)细胞系的活力显著降低。体内研究采用雌性白化小鼠的艾氏模型,在给予分次剂量的γ射线辐射(5 Gy,随后连续5天每天1 Gy)前1小时,用BL(6 mg/kg体重,腹腔注射,每日一次,共10天)进行处理。BL的放射增敏作用明显,表现为肿瘤体积、聚ADP核糖聚合酶-1(PARP-1)、增殖标志物Ki-67和核因子κB活化B细胞(NF-κB)显著减少,而肿瘤细胞中的活性氧(ROS)含量和脂质过氧化(LPO)显著升高。本研究结果为BL的放射增敏作用及其在放疗过程中的潜在应用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f3b/8649096/a5ec0e8e3222/10.1177_15347354211060369-fig1.jpg

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