Division of Pediatric Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
J Pediatr Surg. 2011 Feb;46(2):320-5. doi: 10.1016/j.jpedsurg.2010.11.010.
BACKGROUND/PURPOSE: We have previously reported that the Hedgehog (Hh) signaling pathway is activated in pediatric malignancies. In this study, we examined the effect of the Hh signal inhibitor forskolin on the growth of rhabdomyosarcoma (RMS) in vivo and in vitro and thereby elucidated the possibility of considering Hh signaling pathway as a therapeutic target for RMS.
We evaluated the messenger RNA expressions of Hh signal mediators in 3 human RMS cell lines using reverse transcriptase-polymerase chain reaction method. The effect of forskolin on the tumor cell proliferation was investigated using WST-1 assay (Dojindo Co, Kumamoto, Japan). We inoculated 10(7) tumor cells into the back of nude mice to create RMS xenograft tumor models. Forskolin was subcutaneously administered in the region around the tumor, and the effect on the tumor growth was evaluated.
The messenger RNA expression of glioma-associated oncogene homolog 1, the marker of Hh signaling activation, was expressed at various levels in RMS cell lines. The proliferation of RMS cells was inhibited in a dose-dependent fashion by forskolin. Similarly, in the xenograft model, tumor growth was also significantly reduced by forskolin treatment.
Our findings suggest that the Hh signaling pathway plays an important role in the tumorigenesis of RMS and that this pathway can be considered to be a potential molecular target of new treatment strategies for RMS.
背景/目的：我们之前曾报道过 Hedgehog（Hh）信号通路在儿科恶性肿瘤中被激活。在这项研究中，我们研究了 Hh 信号抑制剂forskolin 对横纹肌肉瘤（RMS）体内和体外生长的影响，从而阐明了将 Hh 信号通路视为 RMS 治疗靶点的可能性。
我们使用逆转录聚合酶链反应方法评估了 3 个人 RMS 细胞系中 Hh 信号介质的信使 RNA 表达。使用 WST-1 测定法（Dojindo Co，熊本，日本）研究 forskolin 对肿瘤细胞增殖的影响。我们将 10（7）个肿瘤细胞接种到裸鼠背部，以建立 RMS 异种移植肿瘤模型。将 forskolin 皮下注射到肿瘤周围区域，并评估其对肿瘤生长的影响。
RMS 细胞系中Glioma-associated oncogene homolog 1（Hh 信号激活的标志物）的信使 RNA 表达水平各异。Forskolin 以剂量依赖性方式抑制 RMS 细胞的增殖。同样，在异种移植模型中，forskolin 治疗也显著降低了肿瘤生长。
我们的研究结果表明，Hh 信号通路在 RMS 的肿瘤发生中起着重要作用，并且该通路可以被视为 RMS 新治疗策略的潜在分子靶标。
