Krüppel-like factor 4 promotes high-mobility group box 1-induced chemotherapy resistance in osteosarcoma cells.
Krüppel-like factor 4 promotes high-mobility group box 1-induced chemotherapy resistance in osteosarcoma cells.
复制标题
Krüppel 样因子 4 促进骨肉瘤细胞中高迁移率组盒 1 诱导的化疗耐药性。
DOI：
10.1111/cas.12864
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发表时间：
2016-03
期刊：
影响因子：
5.7
通讯作者：
Ni J
中科院分区：
文献类型：
--
作者：
Huang J;Liu K;Song D;Ding M;Wang J;Jin Q;Ni J
骨肉瘤是最常见的原发性恶性骨肿瘤，频繁获得化疗耐药性往往是化疗期间取得良好结果的障碍。最近，Krüppel 样因子 4 (KLF4) 已被证明与一些肿瘤的化疗耐药性相关。然而，KLF4 在骨肉瘤细胞化疗耐药中的作用仍不清楚。在这项研究中，定量实时PCR和蛋白质印迹分析显示，骨肉瘤细胞中顺铂、甲氨蝶呤和阿霉素治疗后KLF4表达显着增加，并且KLF4的敲低通过降低细胞克隆形成能力和增加细胞凋亡来增加对这些抗癌药物的敏感性。此外，我们的数据表明，KLF4调节的耐药性可能至少部分地正向调节高迁移率族盒1（HMGB1），在我们之前的研究中发现它是骨肉瘤细胞化疗耐药性的重要贡献者。总之，本研究强调了 KLF4/HMGB1 相互作用在调节化疗耐药中的重要性，并表明靶向 KLF4/高迁移率族蛋白 1 可能是骨肉瘤化疗的一种治疗策略。
Osteosarcoma is the most common primary malignant bone tumor, and the frequent acquisition of chemoresistance is often an obstacle to achieving favorable outcomes during chemotherapy. Recently, Krüppel‐like factor 4 (KLF4) has been shown to be associated with chemotherapy resistance in a few tumors; however, the involvement of KLF4 in chemotherapy resistance in osteosarcoma cells remains unknown. In this study, quantitative real‐time PCR and western blot analysis revealed that KLF4 expression was significantly increased in response to cisplatin, methotrexate and doxorubicin treatment in osteosarcoma cells, and knockdown of KLF4 increased sensitivity to these anticancer drugs by decreasing cellular clonogenic ability and increasing apoptosis. Moreover, our data suggest that KLF4‐regulated drug resistance might, at least partially, positively regulate high‐mobility group box 1 (HMGB1), which was found to be a significant contributor to chemoresistance in osteosarcoma cells in our previous study. In summary, this study highlights the significance of KLF4/HMGB1 interaction in regulating chemotherapy resistance, and suggests that targeting KLF4/high‐mobility group box 1 may be a therapeutic strategy for osteosarcoma chemotherapy.