Qin Xianyun, Zhang Lu, Liu Jilan, Lu Yan, Zhou Fuyao, Jin Feng
Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
Stem Cells Int. 2024 Mar 14;2024:1348269. doi: 10.1155/2024/1348269. eCollection 2024.
Gliomas, the most prevalent primary intracranial tumors, exhibit notable features such as heightened malignancy, rapid recurrence, and elevated mortality rates. Presently, standard therapeutic approaches yield limited curative outcomes. Shikonin, an extract derived from traditional Chinese medicine, demonstrates notable bioactivity against various tumors, including gliomas. This study elucidates Shikonin's capacity to effectively induce necroptosis in glioma cells, concurrently mitigating glioma stemness, as evidenced by diminished levels of stem cell markers, namely SOX2, CD44, CHI3L1, and CD24. Our findings indicate that Shikonin-induced programed necrosis leads to a downregulation of proteasome activity and a decrease in the expression of immune proteasome subunits PSMB8/9/10 and PSME1/2/3, contributing to the attenuation of stemness in gliomas. This study comprehensively investigates the interplay between (immuno)proteasome dynamics, Shikonin-mediated necroptosis, and the consequential reduction in glioma stemness, both in vitro and in vivo. The discussion extends to the potential of Shikonin as a promising therapeutic agent in the management of gliomas, offering a novel avenue for drug development in this challenging clinical context.
胶质瘤是最常见的原发性颅内肿瘤，具有恶性程度高、复发快、死亡率高等显著特征。目前，标准治疗方法的疗效有限。紫草素是一种从传统中药中提取的物质，对包括胶质瘤在内的多种肿瘤具有显著的生物活性。本研究阐明了紫草素有效诱导胶质瘤细胞坏死性凋亡的能力，同时减轻胶质瘤干性，表现为干细胞标志物SOX2、CD44、CHI3L1和CD24水平降低。我们的研究结果表明，紫草素诱导的程序性坏死导致蛋白酶体活性下调，免疫蛋白酶体亚基PSMB8/9/10和PSME1/2/3的表达降低，从而导致胶质瘤干性减弱。本研究全面调查了（免疫）蛋白酶体动力学、紫草素介导的坏死性凋亡以及由此导致的胶质瘤干性降低之间在体外和体内的相互作用。讨论还涉及紫草素作为一种有前景的治疗药物在胶质瘤治疗中的潜力，为这一具有挑战性的临床背景下的药物开发提供了一条新途径。
