State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, No.1, Keyuan Road 4, Gaopeng Street, Chengdu, 610041 Sichuan, China.
J Mol Med (Berl). 2012 Nov;90(11):1311-9. doi: 10.1007/s00109-012-0910-3. Epub 2012 May 31.
Previous studies have suggested that isoliquiritigenin (ISL) has anti-carcinogenic activity in several kinds of solid tumors, however, little is known about the effects of ISL on hematologic malignancies. In this study, we investigated the effects of ISL on multiple myeloma (MM) cells both in vitro and in vivo. The results showed that ISL could inhibit the growth of MM cells and induce their apoptosis in time- and dose-dependent manners. ISL exhibited significant anti-tumor activity in MM xenograft models and synergistically enhanced the anti-myeloma activity of adriamycin. Further analysis demonstrated that ISL not only downregulated IL-6 expression but also significantly decreased levels of phosphorylated ERK and STAT3 and could inhibit phosphorylation levels of ERK and STAT3 induced by recombinant human IL-6, which are critical signaling proteins in IL-6 signaling regulation networks. Taken together, our findings suggested that ISL could inhibit the growth of MM via blocking IL-6 signaling and might serve as a promising therapeutic agent for treatment of MM.
先前的研究表明，甘草查尔酮 B（ISL）在几种实体瘤中具有抗癌活性，然而，关于 ISL 对血液系统恶性肿瘤的影响知之甚少。在这项研究中，我们研究了 ISL 在体外和体内对多发性骨髓瘤（MM）细胞的影响。结果表明，ISL 可以抑制 MM 细胞的生长并诱导其凋亡，且呈时间和剂量依赖性。ISL 在 MM 异种移植模型中表现出显著的抗肿瘤活性，并与阿霉素协同增强抗骨髓瘤活性。进一步分析表明，ISL 不仅下调了 IL-6 的表达，而且还显著降低了磷酸化 ERK 和 STAT3 的水平，并能抑制重组人 IL-6 诱导的 ERK 和 STAT3 的磷酸化水平，这些是 IL-6 信号调节网络中的关键信号蛋白。综上所述，我们的研究结果表明，ISL 通过阻断 IL-6 信号通路抑制 MM 的生长，可能成为治疗 MM 的一种有前途的治疗药物。
