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γ射线联合三氯化镓和/或阿霉素对雌性小鼠艾氏癌的协同疗效。

Synergistic efficacy of γ-radiation together with gallium trichloride and/or doxorubicin against Ehrlich carcinoma in female mice.

作者信息

Kandil Eman, Aziz Nahed Abdel

机构信息

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

Radiation Biology Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.

出版信息

Tumour Biol. 2016 Feb;37(2):1825-34. doi: 10.1007/s13277-015-3954-5. Epub 2015 Aug 29.

Abstract

Combining chemotherapy with radiotherapy represents a key oncology strategy for a more comprehensive attack toward cancers and improves treatment outcome for various solid tumor malignancies. The present study aims to evaluate the synergistic antitumor effect of γ-radiation together with gallium trichloride (GaCl3) and/or doxorubicin (DOX) against solid Ehrlich carcinoma (EC) in female mice. GaCl3 (300 mg/kg body weight (b.w.)) was administered by gavages daily on the seventh day after tumor inoculation, while the cytotoxic drug DOX (4 mg/kg b.w.) was administered intraperitoneally once a week. Whole-body γ-radiation was carried out at a dose 2 Gy once a week. Biochemical analysis showed that solid EC induced a significant increase in malondialdehyde (MDA) content with a significant decrease in the antioxidant state (glutathione peroxidase (GPx) and catalase (CAT) activities) and depleted serum iron concentration compared to normal control. Moreover, a significant increase was observed in calcium level and caspase-3 concentrations in both serum and tumor homogenate respectively associated with a significant alteration in heart, liver, and kidney functions, as compared to control. Treatment of EC-bearing mice with GaCl3and/or DOX combined with γ-radiation exposure significantly reduced tumor volume and displayed a significant improvement in most studied markers which may indicate a synergistic effect of this combination against organ dysfunction and cellular injury. The histopathologically investigation showed that treatment of animals bearing EC with GaCl3and/or DOX with γ-radiation exposure showed shrinkage in tumor lesions and wide zones of apoptotic cells with signs of regenerations. It was concluded that the combination of GaCl3and/or DOX with γ-radiation exposure resulted in super-additive cytotoxic effects on treatment of cancer cells.

摘要

将化疗与放疗相结合是一种关键的肿瘤学策略,可更全面地攻击癌症,并改善各种实体瘤恶性肿瘤的治疗效果。本研究旨在评估γ射线与三氯化镓(GaCl3)和/或阿霉素(DOX)联合对雌性小鼠实体艾氏癌(EC)的协同抗肿瘤作用。在肿瘤接种后第7天,每天通过灌胃给予GaCl3(300 mg/kg体重(b.w.)),而细胞毒性药物DOX(4 mg/kg b.w.)每周腹腔注射一次。全身γ射线照射每周进行一次,剂量为2 Gy。生化分析表明,与正常对照组相比,实体EC导致丙二醛(MDA)含量显著增加,抗氧化状态(谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)活性)显著降低,血清铁浓度降低。此外,与对照组相比,血清和肿瘤匀浆中的钙水平和半胱天冬酶-3浓度均显著升高,同时心脏、肝脏和肾脏功能发生显著改变。用GaCl3和/或DOX联合γ射线照射治疗荷EC小鼠可显著减小肿瘤体积,并且在大多数研究指标上有显著改善,这可能表明这种联合治疗对器官功能障碍和细胞损伤具有协同作用。组织病理学研究表明,用GaCl3和/或DOX联合γ射线照射治疗荷EC动物,肿瘤病变出现萎缩,凋亡细胞区域广泛,并有再生迹象。得出的结论是,GaCl3和/或DOX与γ射线照射联合对癌细胞治疗产生了超相加的细胞毒性作用。

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