Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain.
Department of Pathology, Hospital Complex of Navarra, 31008 Pamplona, Spain.
Int J Oncol. 2021 Mar;58(3):312-330. doi: 10.3892/ijo.2021.5177. Epub 2021 Jan 26.
Glioblastoma is the most malignant brain tumor and presents high resistance to chemotherapy and radiotherapy. Surgery, radiotherapy and chemotherapy with temozolomide are the only treatments against this tumor. New targeted therapies, including epigenetic modulators such as 3‑deazaneplanocin A (DZ‑Nep; an EZH2 inhibitor) and panobinostat (a histone deacetylase inhibitor) are being tested in vitro, together with temozolomide. The present study combined APR‑246 with DZ‑Nep, panobinostat and teomozolomide in order to explore the possibility of restoring p53 function in mutated cases of glioblastoma. Following the Chou‑Talalay method it was demonstrated that APR‑246 acts in an additive manner together with the other compounds, reducing clonogenicity and inducing apoptosis in glioblastoma cells independently of p53 status.
胶质母细胞瘤是最恶性的脑肿瘤，对化疗和放疗具有高度耐药性。手术、替莫唑胺放化疗是目前针对该肿瘤的唯一治疗方法。新的靶向治疗方法，包括表观遗传调节剂如 3-去氮胞苷 A（DZ-Nep；EZH2 抑制剂）和帕比司他（组蛋白去乙酰化酶抑制剂），与替莫唑胺联合应用，正在进行体外试验。本研究将 APR-246 与 DZ-Nep、帕比司他和替莫唑胺联合使用，以探索在突变型胶质母细胞瘤中恢复 p53 功能的可能性。通过 Chou-Talalay 方法证明，APR-246 与其他化合物联合作用呈相加方式，降低克隆形成能力，并独立于 p53 状态诱导胶质母细胞瘤细胞凋亡。
