Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Aug 1;50(8):782-792. doi: 10.1093/abbs/gmy070.
Mantle cell lymphoma (MCL) is an aggressive and mostly incurable B-cell malignancy with frequent relapses after an initial response to standard chemotherapy. Therefore, novel therapies are urgently required to improve MCL clinical outcomes. In this study, MCL cell lines were treated with pterostilbene (PTE), a non-toxic natural phenolic compound primarily found in blueberries. The antitumor activity of PTE was examined by using the Cell Counting Kit-8, apoptosis assays, cell cycle analysis, JC-1 mitochondrial membrane potential assay, western blot analysis, and tumor xenograft models. PTE treatment induced a dose-dependent inhibition of cell proliferation, including the induction of cell apoptosis and cell cycle arrest at the G0/G1 phase. Moreover, the PI3K/Akt/mTOR pathway was downregulated after PTE treatment, which might account for the anti-MCL effects of PTE. Synergistic cytotoxicity was also observed, both in MCL cells and in xenograft mouse models, when PTE was administered in combination with bortezomib (BTZ). The antitumor effects of PTE shown in our study provide an innovative option for MCL patients with poor responses to standardized therapy. It is noteworthy that the treatment combining PTE with BTZ warrants clinical investigation, which may offer an alternative and effective MCL treatment in the future.
套细胞淋巴瘤（MCL）是一种侵袭性且多数不可治愈的 B 细胞恶性肿瘤，在对标准化疗有初始反应后常复发。因此，迫切需要新的疗法来改善 MCL 的临床结局。在这项研究中，用紫檀芪（PTE）处理 MCL 细胞系，紫檀芪是一种主要存在于蓝莓中的无毒天然酚类化合物。通过使用细胞计数试剂盒-8、细胞凋亡检测、细胞周期分析、JC-1 线粒体膜电位检测、western blot 分析和肿瘤异种移植模型来检查 PTE 的抗肿瘤活性。PTE 处理诱导了剂量依赖性的细胞增殖抑制，包括诱导细胞凋亡和细胞周期停滞在 G0/G1 期。此外，PI3K/Akt/mTOR 通路在 PTE 处理后被下调，这可能是 PTE 抗 MCL 的作用机制。当 PTE 与硼替佐米（BTZ）联合给药时，在 MCL 细胞和异种移植小鼠模型中也观察到协同细胞毒性。我们的研究表明 PTE 的抗肿瘤作用为对标准化治疗反应不佳的 MCL 患者提供了一种创新的选择。值得注意的是，PTE 与 BTZ 的联合治疗需要临床研究，这可能为未来提供一种替代和有效的 MCL 治疗方法。
