研究动态
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阿霉素和聚乙二醇化透明质酸酶对大鼠脑肿瘤模型的抗肿瘤作用特征。

Characteristics of the Antitumor Effect of Doxorubicin and Pegylated Hyaluronidase on Models of Rat Brain Tumors.

发表日期:2024 Jul 04
作者: V V Kudelkina, Ts Magsarzhav, A M Kosyreva, A P Nadeev, P G Madonov, A I Alekseeva, E A Miroshnichenko, I V Arutyunyan
来源: Brain Structure & Function

摘要:

透明质酸酶通过裂解透明质酸(细胞外基质的主要成分)来增加组织通透性和细胞外液的扩散。透明质酸酶聚乙二醇化 (Hyal-PEG) 会降低其清除率并增强生物分布。在体外(大鼠胶质母细胞瘤 101.8 球体的形态学分析)和体内(通过肿瘤脑内移植后大鼠的存活时间和形态学分析)研究了 Hyal-PEG 以及 Hyal-PEG 与阿霉素组合的促癌和抗癌活性。分析)。体外培养基中存在阿霉素和 Hyal-PEG 时,球体失去粘附基质并分解成单个细胞的能力。用 Hyal-PEG 进行肿瘤组织脑内移植并没有加速胶质母细胞瘤的生长。接受单独肿瘤移植和联合Hyal-PEG移植的动物的平均存活时间分别为13天和20天。在一只移植肿瘤和 Hyal-PEG 的大鼠中,该参数增加了 53%。接受阿霉素和Hyal-PEG全身治疗的大鼠的存活时间显着增加(p=0.003)。治疗剂量的阿霉素联合 Hyal-PEG 的抗肿瘤作用在体外大鼠胶质母细胞瘤 101.8 模型上得到证实。 Hyal-PEG抑制肿瘤细胞的粘附,但不导致其死亡。 Hyal-PEG 处理的肿瘤移植不会缩短动物的存活时间。全身给予治疗剂量的阿霉素和 Hyal-PEG 可延长胶质母细胞瘤大鼠的生存时间 101.8.© 2024。Springer Science Business Media, LLC,Springer Nature 旗下公司。
Hyaluronidase increases tissue permeability and diffusion of the extracellular fluid by cleaving hyaluronan, the primary component of the extracellular matrix. Hyaluronidase pegylation (Hyal-PEG) decreases its clearance and enhances biodistribution. The pro- and anticancer activity of Hyal-PEG and a combination of Hyal-PEG with doxorubicin were studied in vitro (morphological analysis of rat glioblastoma 101.8 spheroids) and in vivo (by the survival time of rats after intracerebral transplantation of the tumor and morphological analysis). In the presence of doxorubicin and Hyal-PEG in the culture medium in vitro, spheroids lost their ability to adhere to the substrate and disintegrate into individual cells. Intracerebral transplantation of the tumor tissue with Hyal-PEG did not accelerate glioblastoma growth. The mean survival time for animals receiving transplantation of the tumor alone and in combination with Hyal-PEG was 13 and 20 days, respectively. In one rat with transplanted tumor and Hyal-PEG, this parameter increased by 53%. The survival time of rats receiving systemic therapy with doxorubicin and Hyal-PEG significantly increased (p=0.003). Antitumor effect of therapeutic doses of doxorubicin combined with Hyal-PEG was demonstrated on the model of rat glioblastoma 101.8 in vitro. Hyal-PEG inhibited adhesion of tumor cells, but did not cause their death. Transplantation of Hyal-PEG-treated tumor did not reduce animal survival time. Systemic administration of therapeutic doses of doxorubicin with Hyal-PEG increased survival time of rats with glioblastoma 101.8.© 2024. Springer Science+Business Media, LLC, part of Springer Nature.