FOXM1-CD44 信号通路对于人肝癌细胞获得regorafenib 耐药性至关重要。

FOXM1-CD44 Signaling Is Critical for the Acquisition of Regorafenib Resistance in Human Liver Cancer Cells.

机构信息

Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

出版信息

Int J Mol Sci. 2022 Jul 14;23(14):7782. doi: 10.3390/ijms23147782.

Regorafenib is a multikinase inhibitor that was approved by the US Food and Drug administration in 2017. Cancer stem cells (CSCs) are a small subset of cancer-initiating cells that are thought to contribute to therapeutic resistance. The forkhead box protein M1 (FOXM1) plays an important role in the regulation of the stemness of CSCs and mediates resistance to chemotherapy. However, the relationship between FOXM1 and regorafenib resistance in liver cancer cells remains unknown. We found that regorafenib-resistant HepG2 clones overexpressed FOXM1 and various markers of CSCs. Patients with hepatocellular carcinoma also exhibited an upregulation of FOXM1 and resistance to regorafenib, which were correlated with a poor survival rate. We identified a close relationship between FOXM1 expression and regorafenib resistance, which was correlated with the survival of patients with hepatocellular carcinoma. Thus, a strategy that antagonizes FOXM1-CD44 signaling would enhance the therapeutic efficacy of regorafenib in these patients.

瑞戈非尼是一种多激酶抑制剂，于 2017 年获得美国食品和药物管理局批准。癌症干细胞（CSC）是一小部分起始癌症的细胞，被认为有助于治疗抵抗。叉头框蛋白 M1（FOXM1）在调节 CSC 的干性中起重要作用，并介导对化疗的耐药性。然而，FOXM1 与肝癌细胞中的瑞戈非尼耐药性之间的关系尚不清楚。我们发现，瑞戈非尼耐药的 HepG2 克隆过表达 FOXM1 和各种 CSC 标志物。肝癌患者也表现出 FOXM1 的上调和对瑞戈非尼的耐药性，这与生存率降低有关。我们确定了 FOXM1 表达与瑞戈非尼耐药性之间的密切关系，这与肝癌患者的生存有关。因此，拮抗 FOXM1-CD44 信号的策略将增强这些患者接受瑞戈非尼治疗的疗效。