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咖啡因通过抑制 AKT/mTOR/S6K、NF-κB 和 MAPK 通路诱导骨肉瘤细胞凋亡。

Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF-κB and MAPK pathways.

机构信息

Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.

出版信息

Anticancer Res. 2012 Sep;32(9):3643-9.

PMID:22993301
Abstract

We previously reported that caffeine-assisted chemotherapy improved the treatment of malignant bone and soft tissue tumours such as osteosarcoma. Caffeine affects tumour cells through various pathways, including phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT, Bcl-2-associated X protein (BAX), caspase-3 and p53, and has therefore been indicated as being useful for the treatment of malignant tumours. Here, the effects of caffeine on the proliferation of HOS osteosarcoma cells were assessed by WST-8 assay, and the effects on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways were assessed by western blot analyses. Caffeine inhibited proliferation of HOS cells and suppressed NF-κB, AKT, mTOR/S6K and ERK activities. Our results support those from previous studies relating to the use of caffeine in the treatment of osteosarcoma.

摘要

我们之前报道过,咖啡因辅助化疗可改善骨肉瘤等恶性骨和软组织肿瘤的治疗效果。咖啡因通过多种途径影响肿瘤细胞,包括磷酸酶和张力蛋白同源物缺失的染色体 10(PTEN)、AKT、Bcl-2 相关 X 蛋白(BAX)、半胱天冬酶-3 和 p53,因此被认为对恶性肿瘤的治疗有用。在这里,通过 WST-8 测定评估了咖啡因对 HOS 骨肉瘤细胞增殖的影响,并通过 Western blot 分析评估了咖啡因对核因子 kappa-轻链增强子的激活 B 细胞(NF-κB)、雷帕霉素(mTOR)和丝裂原激活蛋白激酶(MAPK)途径的影响。咖啡因抑制了 HOS 细胞的增殖,并抑制了 NF-κB、AKT、mTOR/S6K 和 ERK 的活性。我们的结果支持了之前关于咖啡因在骨肉瘤治疗中的应用的研究结果。

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