Anticancer Non-narcotic Opium Alkaloid Papaverine Suppresses Human Glioblastoma Cell Growth

Anticancer Non-narcotic Opium Alkaloid Papaverine Suppresses Human Glioblastoma Cell Growth
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DOI:
10.21873/anticanres.13889
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发表时间:
2019-12-01
影响因子:
2
通讯作者:
Tanuma, Sei-Ichi
Tanuma, Sei-Ichi
中科院分区:
医学4区
文献类型:
--
作者:
Inada, Mana;Sato, Akira;Tanuma, Sei-Ichi

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背景:胶质母细胞瘤(GBM)是最具侵袭性的原发性恶性脑肿瘤。高迁移率族蛋白 1 (HMGB1) 和晚期糖基化终产物受体 (RAGE) 之间的相互作用对于肿瘤细胞生长非常重要。此前,我们发现了一种抗癌候选药物罂粟碱,它可以抑制 HMGB1-RAGE 相互作用。材料和方法:我们的研究使用克隆形成试验以及 U87MG 异种移植小鼠模型评估了罂粟碱单独使用或与替莫唑胺联合使用对 U87MG 和 T98G 人 GBM 细胞的抗癌作用。罂粟碱的放射增敏功效是根据 T98G 细胞的克隆性来测量的。结果:罂粟碱显着抑制U87MG和T98G细胞的克隆形成。与单一治疗相比,罂粟碱和替莫唑胺的组合在 U87MG 异种移植小鼠模型中更高度抑制 T98G 细胞的克隆形成并延迟肿瘤生长。此外,罂粟碱增加了T98G细胞的放射敏感性。结论:罂粟碱是治疗 GBM 的潜在抗癌药物。
Background: Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumour. The interaction between high-mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) is important for tumour cell growth. Previously, we identified an anticancer candidate, papaverine, that inhibited the HMGB1-RAGE interaction. Materials and Methods: Our study assessed the anticancer effects of papaverine alone or in combination with temozolomide on U87MG and T98G human GBM cells using clonogenicity assays, as well as in a U87MG xenograft mouse model. The radiosensitizing efficacy of papaverine was measured based on the clonogenicity of T98G cells. Results: Papaverine significantly inhibited the clonogenicity of U87MG and T98G cells. Compared with single treatment, the combination of papaverine and temozolomide more highly suppressed the clonogenicity of T98G cells and delayed tumour growth in the U87MG xenograft mouse model. Furthermore, papaverine increased the radiosensitivity of T98G cells. Conclusion: Papaverine is a potential anticancer drug in GBM treatment.