替莫唑胺
自噬
顺铂
神经母细胞瘤
医学
化疗
羟基氯喹
癌症研究
达卡巴嗪
细胞凋亡
药理学
癌症
肿瘤科
内科学
生物
细胞培养
2019年冠状病毒病(COVID-19)
遗传学
疾病
传染病(医学专业)
生物化学
作者
Darcy Wear,Eesha Bhagirath,Andithangal Venkatesan Balachandar,Caleb Vegh,Siyaram Pandey
标识
DOI:10.3390/ijms241512052
摘要
Neuroblastoma is the most common tumour in children under 1 year old, accounting for 12–15% of childhood cancer deaths. Although current treatments are relatively efficacious against this cancer, associated adverse effects could be detrimental to growth and development. In contrast, glioblastoma accounts for 52% of brain tumours and has an extremely poor prognosis. Current chemotherapeutics include temozolomide, which has numerous negative side-effects and a low-effective rate. Previous studies have shown the manipulation of autophagy to be a promising method for targeting cancers, including glioblastoma. We sought to determine the effects of autophagic alterations in combination with current chemotherapies in both neuroblastoma and glioblastoma. Supplementing cisplatin or temozolomide with autophagy activator rapamycin stabilized cancer cell mitochondria, despite having little effect on apoptosis or oxidative stress. Autophagy inhibition via 3-methyladenine or hydroxychloroquine alongside standard chemotherapies enhanced apoptosis and oxidative stress, with 3-methyladenine also disrupting mitochondrial health. Importantly, combining hydroxychloroquine with 0.5 µM cisplatin or 50 µg/mL temozolomide was as or more effective than 2 µM cisplatin or 100 µg/mL temozolomide alone. Analyzing these interesting results, a combined treatment of autophagy inhibitor with a standard chemotherapeutic agent could help to improve patient prognosis and reduce chemotherapy doses and their associated side-effects.
科研通智能强力驱动
Strongly Powered by AbleSci AI