Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, P.R. China.
Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, P.R. China.
Oncol Res. 2019 Mar 29;27(4):475-486. doi: 10.3727/096504018X15270916676926. Epub 2018 May 24.
Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ.
脑胶质瘤是中枢神经系统最常见的恶性肿瘤，具有复发率和死亡率高、预后差等特点。蟾酥是一种从蟾蜍毒液中提取的中药，其中的主要成分之一是华蟾酥毒基。已有研究表明，华蟾酥毒基对多种肿瘤细胞具有抑制作用。为了验证华蟾酥毒基对神经胶质瘤细胞和神经胶质瘤干细胞（GSCs）的抑制作用，并探讨其作用机制，本研究采用 MTT 和集落形成实验检测华蟾酥毒基处理后神经胶质瘤细胞的增殖情况。此外，我们还通过流式细胞术、Western blot 和逆转录聚合酶链反应（RT-PCR）分析来研究华蟾酥毒基是否能抑制或杀死 GSCs。最后，我们还研究了华蟾酥毒基是否能提高替莫唑胺（TMZ）的治疗效果，并探讨了其作用机制。综上所述，本研究数据表明华蟾酥毒基能够抑制神经胶质瘤细胞的生长和增殖，抑制 GSCs 的增殖并杀死 GSCs。华蟾酥毒基通过上调凋亡蛋白 cleaved caspase 3 和多聚（ADP-核糖）聚合酶（PARP）的表达，下调端粒酶活性标志物人类端粒酶逆转录酶的表达，诱导 GSCs 凋亡。此外，华蟾酥毒基还通过激活线粒体凋亡途径增强 TMZ 对 GSCs 的抑制作用。这些结果提示华蟾酥毒基可损伤 GSCs，诱导其凋亡，并增强 GSCs 对 TMZ 的敏感性。
