Turk J Med Sci. 2015;45(1):38-46. doi: 10.3906/sag-1401-127.
BACKGROUND/AIM: In this study, the in vitro and in vivo effectiveness of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) in combination with bortezomib, a proteasome inhibitor, was explored in multiple myeloma (MM) cells.
The cytotoxic effects of CAPE and bortezomib were determined by XTT cell proliferation assay. Apoptosis levels were analyzed with annexin V-fluorescein isothiocyanate, nuclear factor kappa beta (NF-κB) was analyzed with electrophoretic mobility-shift assay, and interleukin (IL)-6 levels were analyzed with enzyme-linked immunosorbent assay to evaluate CAPE's mechanism of action. To investigate the in vivo effectiveness of CAPE and bortezomib, an experimental plasmacytoma model was induced in BALB/c mice.
Increasing concentrations of CAPE and bortezomib decreased the proliferation of ARH-77 cells in a dose-dependent manner. With doses of CAPE IC50, a significant increase in apoptosis and a significant decrease in IL-6 levels were detected. The NF-κB DNA- binding activity decreased compared to the basal ARH-77 level. The administration of CAPE alone or in combination with bortezomib increased the rate of survival compared to the control group.
We think that our study, which is the first to demonstrate the in vitro and in vivo effectiveness of the.combined use of CAPE and bortezomib, will be a pioneer for future human applications of CAPE in MM.
背景/目的：在这项研究中，我们探索了咖啡酸苯乙酯（CAPE）与蛋白酶体抑制剂硼替佐米联合应用在多发性骨髓瘤（MM）细胞中的体外和体内疗效。
通过 XTT 细胞增殖试验测定 CAPE 和硼替佐米的细胞毒性作用。用 Annexin V-异硫氰酸荧光素分析细胞凋亡水平，用电泳迁移率变动分析检测核因子 kappa B（NF-κB），用酶联免疫吸附试验检测白细胞介素（IL）-6 水平，以评估 CAPE 的作用机制。为了研究 CAPE 和硼替佐米的体内疗效，我们在 BALB/c 小鼠中诱导了实验性浆细胞瘤模型。
CAPE 和硼替佐米的浓度增加，ARH-77 细胞的增殖呈剂量依赖性下降。在 CAPE 的 IC50 剂量下，检测到凋亡显著增加，IL-6 水平显著降低。与基础 ARH-77 水平相比，NF-κB DNA 结合活性降低。与对照组相比，单独使用 CAPE 或与硼替佐米联合使用均可提高存活率。
我们认为，我们的研究首次证明了 CAPE 与硼替佐米联合应用的体外和体内疗效，这将为未来 CAPE 在 MM 中的人类应用开辟先河。
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