Department of Human Anatomy, Histology and Embryology, Shandong University School of Medicine, Jinan, 250012, PR China; Department of Stomatology, Liaocheng People's Hospital, Liaocheng, 252000, PR China; Shandong Province Key Laboratory of Oral and Maxillofacial-Head and Neck Medicine, Liaocheng, 252000, PR China.
Department of Stomatology, Liaocheng People's Hospital, Liaocheng, 252000, PR China; Shandong Province Key Laboratory of Oral and Maxillofacial-Head and Neck Medicine, Liaocheng, 252000, PR China.
Mol Cell Probes. 2019 Apr;44:57-62. doi: 10.1016/j.mcp.2019.02.004. Epub 2019 Feb 22.
CDKL1 is a cyclin-dependent kinase-like kinase that is highly expressed in diverse types of cancer cells. However, the role of CDKL1 in the chemoresistance of oral squamous cell carcinoma (OSCC) remains largely undefined. Here, we explored the role of CDKL1 in the chemoresistance of the human OSCC cell line CAL27 to hydroxycamptothecin (HCPT). Real-time quantitative polymerase chain reaction and western blotting revealed that exposure of CAL27 cells to HCPT led to a marked increase in the expression of CDKL1 at the mRNA and protein levels. Knockdown of CDKL1 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest in CAL27 cells based on the results of MTT and flow cytometry assays, respectively. CAL27 cells displayed attenuated biological activity of the cell population. After treatment with HCPT, whereas CDKL1 overexpression increased the resistance to HCPT of the remaining cells. Moreover, the western blot showed that the expression of cleaved-caspase 3 and phosphorylated ataxia telangiectasia mutated proteins was upregulated by HCPT treatment in CAL27 cells. Furthermore, CDKL1 overexpression partially reversed the inhibitory effects of HCPT in CAL27 cells. These results suggest that CDKL1 overexpression decreased the chemosensitivity of OSCC cells to HCPT, indicating a potential strategic approach for reversing the HCPT resistance in human OSCC.
CDKL1 是一种细胞周期依赖性激酶样激酶，在多种类型的癌细胞中高度表达。然而，CDKL1 在口腔鳞状细胞癌（OSCC）化疗耐药中的作用在很大程度上尚未确定。在这里，我们探讨了 CDKL1 在人 OSCC 细胞系 CAL27 对羟基喜树碱（HCPT）化疗耐药中的作用。实时定量聚合酶链反应和 Western blot 显示，CAL27 细胞暴露于 HCPT 导致 CDKL1 在 mRNA 和蛋白水平的表达明显增加。MTT 和流式细胞术检测分别显示，CDKL1 敲低显著抑制 CAL27 细胞的增殖，并诱导细胞周期 G0/G1 期阻滞。CAL27 细胞的群体生物学活性减弱。用 HCPT 处理后，CDKL1 过表达增加了剩余细胞对 HCPT 的耐药性。此外，Western blot 显示，CAL27 细胞中 HCPT 处理后 cleaved-caspase 3 和磷酸化 ataxia telangiectasia 突变蛋白的表达上调。此外，CDKL1 过表达部分逆转了 HCPT 对 CAL27 细胞的抑制作用。这些结果表明，CDKL1 过表达降低了 OSCC 细胞对 HCPT 的化疗敏感性，表明逆转人 OSCC 中 HCPT 耐药性的一种潜在策略。
