Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Scientific Research, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
J Ethnopharmacol. 2020 Oct 28;261:113071. doi: 10.1016/j.jep.2020.113071. Epub 2020 Jun 27.
Xihuang pill, as a famous traditional Chinese medicine formula, is used for tumor treatment in China. The anti-tumor activities and mechanisms of Xihuang pill still remain unclear.
The Akt/mTOR signaling pathway plays an important role in mediating cell proliferation and apoptosis in glioblastoma. This study aimed to investigate whether Xihuang pill could potentiate temozolomide-induced apoptosis of glioblastoma U87 and U251 cells in vivo and its underlying mechanisms related to Akt/mTOR pathway.
Human glioblastoma U87 and U251 xenograft models were established. Immunocytochemistry and Western blot were performed to evaluate the anti-proliferative effect, apoptosis and Akt/mTOR signaling mediators.
The results showed that Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone inhibited tumor growth in glioblastoma U87 and U251 xenografts. When Xihuang pill (1 g/kg) and temozolomide (10 mg/kg) were co-administrated, the activities of antitumor growth were markedly increased. Meanwhile, Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone decreased the levels of Ki67 and PCNA expression in glioblastoma U87 and U251 xenografts. In combination treatment group, the inhibitory effects on Ki67 and PCNA expression were significantly enhanced in glioblastoma U87 and U251 xenografts compared to temozolomide treatment alone. Examining the apoptotic index by TUNEL assay showed similar results. Furthermore, Xihuang pill markedly down-regulated the Bcl-2/Bax ratio and inhibited the activation of Akt/mTOR pathway in glioblastoma U87 and U251 xenografts. In addition, no significant signs of toxicities were related to Xihuang pill and/or temozolomide treatment.
The present study suggested that Xihuang pill might potentiate temozolomide-induced apoptosis of glioblastoma cells in vivo through inhibiting Akt/mTOR-dependent pathway.
西黄丸是一种著名的中药方剂，在中国用于肿瘤治疗。西黄丸的抗肿瘤活性和机制仍不清楚。
Akt/mTOR 信号通路在介导胶质母细胞瘤细胞增殖和凋亡中起着重要作用。本研究旨在探讨西黄丸是否能增强替莫唑胺诱导的体内 U87 和 U251 胶质母细胞瘤细胞凋亡及其与 Akt/mTOR 通路相关的潜在机制。
建立人胶质母细胞瘤 U87 和 U251 异种移植模型。免疫细胞化学和 Western blot 用于评估抗增殖作用、凋亡和 Akt/mTOR 信号转导介质。
结果表明，西黄丸（0.5、1g/kg）或替莫唑胺（10mg/kg）单独治疗均可抑制 U87 和 U251 胶质母细胞瘤异种移植瘤的生长。当西黄丸（1g/kg）和替莫唑胺（10mg/kg）联合使用时，抗肿瘤生长的活性明显增加。同时，西黄丸（0.5、1g/kg）或替莫唑胺（10mg/kg）单独治疗可降低 U87 和 U251 胶质母细胞瘤异种移植瘤中 Ki67 和 PCNA 的表达水平。在联合治疗组中，与替莫唑胺单独治疗相比，U87 和 U251 胶质母细胞瘤异种移植瘤中 Ki67 和 PCNA 表达的抑制作用明显增强。通过 TUNEL 检测凋亡指数也得到了类似的结果。此外，西黄丸明显下调了 Bcl-2/Bax 比值，并抑制了 Akt/mTOR 通路在 U87 和 U251 胶质母细胞瘤异种移植瘤中的激活。此外，西黄丸和/或替莫唑胺治疗与无明显毒性相关。
本研究表明，西黄丸可能通过抑制 Akt/mTOR 依赖性途径增强替莫唑胺诱导的体内胶质母细胞瘤细胞凋亡。
