Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, Italy.
Kitos Biotech Srls, Tramariglio, 07041 Alghero, Italy.
Int J Mol Sci. 2022 Mar 25;23(7):3581. doi: 10.3390/ijms23073581.
Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological approach to inhibit MYC in cancer cells is represented by Bromodomain and Extra-Terminal motif (BET) protein inhibitors. In this paper, we evaluated the effects of BET inhibitor (+)-JQ1 (JQ1) on the viability of aRMS and eRMS cells. Interestingly, we found that the drug sensitivity of RMS cell lines to JQ1 was directly proportional to the expression of MYC. JQ1 induces G1 arrest in cells with the highest steady-state levels of MYC, whereas apoptosis is associated with MYC downregulation. These findings suggest BET inhibition as an effective strategy for the treatment of RMS alone or in combination with other drugs.
横纹肌肉瘤（RMS）是最常见的小儿软组织肉瘤类型。它分为两个主要亚型：胚胎型（eRMS）和肺泡型（aRMS）。MYC 家族蛋白在 RMS 肿瘤中经常高度表达，高水平与预后不良相关。抑制癌细胞中 MYC 的药理学方法是通过溴结构域和末端结构域（BET）蛋白抑制剂来实现的。在本文中，我们评估了 BET 抑制剂（+）-JQ1（JQ1）对 aRMS 和 eRMS 细胞活力的影响。有趣的是，我们发现 RMS 细胞系对 JQ1 的药物敏感性与 MYC 的表达直接成正比。JQ1 在 MYC 稳态水平最高的细胞中诱导 G1 期停滞，而凋亡与 MYC 下调相关。这些发现表明 BET 抑制作为单独治疗 RMS 或与其他药物联合治疗的有效策略。
