Huang He, Song Jian, Liu Zheng, Pan Li, Xu Guozheng
Department of Neurosurgery, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Neurosurgery, Wuhan General Hospital of PLA, Wuhan, Hubei 430070, P.R. China.
Oncol Lett. 2018 Feb;15(2):1487-1494. doi: 10.3892/ol.2017.7446. Epub 2017 Nov 20.
Glioblastomas are the most common primary and malignant brain tumors. The standard therapy includes surgery and radiotherapy plus chemotherapy, with additional bevacizumab to block the angiogenesis in tumors. However, the ever-growing tolerance of glioblastomas to chemotherapeutic drugs impairs the clinical outputs of tumor treatment. The present study investigated the tolerance of glioblastomas to bevacizumab. Although bevacizumab resulted in direct anti-proliferation and pro-apoptosis effects on glioblastoma cells via downregulating the anti-apoptotic proteins and upregulating the pro-apoptotic proteins, tolerance was also encountered that was mainly caused by autophagy induction in tumor cells. The suppressed Akt-mTOR signaling pathway led to the upregulated autophagy process. Blockade of the autophagy process significantly increased the tumor-suppressive effect of bevacizumab on glioblastoma cells. To our knowledge, the present study is the first to report the involvement of autophagy in the tolerance of glioblastomas to bevacizumab. Therefore, autophagy inhibition may be considered a novel way to overcome the tolerance of glioblastomas to anti-angiogenic agents.
胶质母细胞瘤是最常见的原发性恶性脑肿瘤。标准治疗包括手术、放疗加化疗，外加贝伐单抗以阻断肿瘤血管生成。然而，胶质母细胞瘤对化疗药物的耐受性不断增加，损害了肿瘤治疗的临床效果。本研究调查了胶质母细胞瘤对贝伐单抗的耐受性。尽管贝伐单抗通过下调抗凋亡蛋白和上调促凋亡蛋白对胶质母细胞瘤细胞产生直接的抗增殖和促凋亡作用，但也出现了耐受性，这主要是由肿瘤细胞中的自噬诱导引起的。Akt-mTOR信号通路的抑制导致自噬过程上调。阻断自噬过程显著增强了贝伐单抗对胶质母细胞瘤细胞的肿瘤抑制作用。据我们所知，本研究是首次报道自噬参与胶质母细胞瘤对贝伐单抗的耐受性。因此，抑制自噬可能被认为是克服胶质母细胞瘤对抗血管生成药物耐受性的一种新方法。
