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对光动力疗法耐药的人胶质母细胞瘤细胞的分离与初步表征

Isolation and initial characterization of human glioblastoma cells resistant to photodynamic therapy.

作者信息

Vilchez María L, Rodríguez Lucía B, Palacios Rodrigo E, Prucca César G, Caverzán Matías D, Caputto Beatriz L, Rivarola Viviana A, Milla Sanabria Laura N

机构信息

Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto (UNRC), INBIAS, CONICET-UNRC, Río Cuarto, 5800, Córdoba, Argentina.

Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto (UNRC), IITEMA, CONICET-UNRC, Río Cuarto, 5800, Córdoba, Argentina.

出版信息

Photodiagnosis Photodyn Ther. 2021 Mar;33:102097. doi: 10.1016/j.pdpdt.2020.102097. Epub 2020 Nov 21.

DOI:10.1016/j.pdpdt.2020.102097
PMID:33232818
Abstract

Glioblastoma is the most severe form of brain cancer. Despite multimodal therapy combining surgery, radiotherapy and chemotherapy, prognosis of patients is dismal. It has been observed that the surgical resection guided by photosensitizer fluorescence followed by photodynamic therapy (PDT) prolongs the average survival in patients with glioblastoma. The main problem with all oncological treatments, including PDT, is the presence of resistant cells. The objective of this study was to isolate and perform an initial characterization of human glioblastoma cells resistant to PDT employing methyl-5-aminolevulinic acid. We obtained resistant cells from the T98 G cell line. Resistant populations accumulated less photosensitizer, formed spheroids of higher number of cells, had higher tumorigenic capacity, and expressed higher mRNA levels of fibroblastic growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and β-platelet-derived growth factor receptor (βPDGFR) than parental cells. The studies of glioblastoma resistance to PDT would help to better understand the causes of tumor recurrence after PDT and to develop new therapeutic proposals in this field of oncology.

摘要

胶质母细胞瘤是最严重的脑癌形式。尽管采用了手术、放疗和化疗相结合的多模式治疗,但患者的预后仍然很差。据观察,在光敏剂荧光引导下进行手术切除,随后进行光动力疗法(PDT),可延长胶质母细胞瘤患者的平均生存期。包括PDT在内的所有肿瘤治疗的主要问题是存在耐药细胞。本研究的目的是分离并初步鉴定对使用5-氨基乙酰丙酸的PDT具有抗性的人胶质母细胞瘤细胞。我们从T98 G细胞系中获得了耐药细胞。与亲代细胞相比,耐药群体积累的光敏剂较少,形成的细胞球数量更多,具有更高的致瘤能力,并且成纤维细胞生长因子受体(FGFR)、表皮生长因子受体(EGFR)和β-血小板衍生生长因子受体(βPDGFR)的mRNA水平更高。对胶质母细胞瘤对PDT耐药性的研究将有助于更好地理解PDT后肿瘤复发的原因,并在该肿瘤学领域开发新的治疗方案。

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