Zhou Qiao
School of Public Affairs, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Onco Targets Ther. 2015 Apr 2;8:689-97. doi: 10.2147/OTT.S80047. eCollection 2015.
Glioma is the most common type of primary brain tumor. Despite the combination of surgery, chemotherapy, and radiotherapy, the median survival duration of patients with malignant glioma is still very short. Temozolomide (TMZ) is the primary and most promising therapeutic drug for glioma; however, it is easy to develop acquired resistance during treatment. Activation of receptor tyrosine kinases (RTKs) has been identified to be involved in the acquisition of resistance toward many anticancer drugs. So inhibition of RTKs might be a promising therapeutic strategy for overcoming or attenuating acquired drug resistance. Here, we have investigated the anticancer activities of BMS-536924, an ATP-competitive IGF-1R/IR inhibitor in glioma, especially TMZ-resistant glioma, both in vitro and in vivo. We found that BMS-536924 could effectively reduce viability of both TMZ-sensitive and -resistant glioma cells. BMS-536924 induced dramatic apoptosis in TMZ-resistant cells, and it also dramatically inhibited migration of TMZ-resistant cells. Importantly, BMS-536924 significantly suppressed glioma tumor growth in vivo. This is the first report on anticancer activity of BMS-536924 in glioma. BMS-536924 is a promising compound in the therapy of glioma, especially of TMZ-resistant glioma, which might shed new light on glioma therapy.
神经胶质瘤是最常见的原发性脑肿瘤类型。尽管采用了手术、化疗和放疗相结合的治疗方法，但恶性神经胶质瘤患者的中位生存期仍然很短。替莫唑胺（TMZ）是治疗神经胶质瘤的主要且最有前景的治疗药物；然而，在治疗过程中很容易产生获得性耐药。已确定受体酪氨酸激酶（RTK）的激活与对许多抗癌药物的耐药性获得有关。因此，抑制RTK可能是克服或减轻获得性耐药的一种有前景的治疗策略。在此，我们研究了ATP竞争性IGF-1R/IR抑制剂BMS-536924在神经胶质瘤，尤其是TMZ耐药神经胶质瘤中的体内外抗癌活性。我们发现BMS-536924可以有效降低TMZ敏感和耐药神经胶质瘤细胞的活力。BMS-536924在TMZ耐药细胞中诱导显著凋亡，并且还显著抑制TMZ耐药细胞的迁移。重要的是，BMS-536924在体内显著抑制神经胶质瘤肿瘤生长。这是关于BMS-536924在神经胶质瘤中抗癌活性的首次报道。BMS-536924是治疗神经胶质瘤，尤其是TMZ耐药神经胶质瘤的一种有前景的化合物，这可能为神经胶质瘤治疗带来新的思路。
