Colapietro Alessandro, Yang Peiying, Rossetti Alessandra, Mancini Andrea, Vitale Flora, Chakraborty Sharmistha, Martellucci Stefano, Marampon Francesco, Mattei Vincenzo, Gravina Giovanni Luca, Iorio Roberto, Newman Robert A, Festuccia Claudio
Laboratory of Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Front Pharmacol. 2022 Mar 23;13:852941. doi: 10.3389/fphar.2022.852941. eCollection 2022.
Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from , as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties. Here we demonstrate that PBI-05204 treatment leads to an increase in the sensitivity of GBM cells to radiation in which the main mechanisms are the transition from autophagy to apoptosis, enhanced DNA damage and reduced DNA repair after radiotherapy (RT) administration. The combination of PBI-05204 with RT was associated with reduced tumor progression evidenced by both subcutaneous as well as orthotopic implanted GBM tumors. Collectively, these results reveal that PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that PBI-05204 has already been examined in Phase I and II clinical trials for cancer patients, its efficacy when combined with standard-of-care radiotherapy regimens in GBM should be explored.
多形性胶质母细胞瘤（GBM）是最常见且恶性程度最高的脑癌类型之一。尽管在开发治疗GBM的新疗法方面取得了进展，但它在很大程度上仍然无法治愈，预后较差，预期寿命很短。最近的研究表明，夹竹桃麻素（一种源自夹竹桃科植物的独特强心苷）以及含有该分子的特定提取物（PBI - 05204）可抑制人胶质母细胞瘤的生长，并调节胶质母细胞瘤患者来源的干细胞更新特性。在此，我们证明PBI - 05204治疗可提高GBM细胞对辐射的敏感性，其主要机制是放疗（RT）给药后从自噬向凋亡的转变、增强的DNA损伤和减少的DNA修复。PBI - 05204与RT联合使用与皮下和原位植入的GBM肿瘤所证实的肿瘤进展减少相关。总体而言，这些结果表明PBI - 05204在人GBM的临床前/小鼠模型中增强了RT的抗肿瘤活性。鉴于PBI - 05204已在癌症患者的I期和II期临床试验中进行了研究，应探索其与GBM标准护理放疗方案联合使用时的疗效。
