2. Academic Validation
  3. Camptothecin induced DDX5 degradation increased the camptothecin resistance of osteosarcoma

Camptothecin induced DDX5 degradation increased the camptothecin resistance of osteosarcoma

  • Exp Cell Res. 2020 Sep 15;394(2):112148. doi: 10.1016/j.yexcr.2020.112148.
Xingkai Zhao 1,  Miao Bao 2,  Fengmin Zhang 3,  Wenbo Wang 4
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 2 The First Affiliated Hospital of Xi'an Medical University, China.
  • 3 Department of Microbiology, Harbin Medical University, Harbin, China. Electronic address: 15636837116@163.com.
  • 4 Department of Orthopedic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: wangwenbo@hrbmu.edu.cn.
PMID: 32585151 DOI: 10.1016/j.yexcr.2020.112148
Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Unfortunately, chemo-resistance is a huge obstacle in the treatment of OS. However, the underlying molecular mechanisms of OS chemo-resistance still remain unknown. Here we reported that the resistance to camptothecin (cpt) therapy was driven by degradation of DDX5. DDX5 knockdown decreased cell death and DNA damage and recovered cell proliferation in cpt treated 143B cells. Furthermore, we found that DDX5 bound to NONO, a kind of DNA repairing protein, and regulated NONO functions. Our data verified that cpt-induced degradation of DDX5 following by breaking down the protein bound of NONO, which participated in the resistance of cpt. In the summary, according to our results, DDX5 might be a potential therapeutic target for improving clinical outcomes of cpt in OS.

Keywords

Camptothecin; DDX5; Osteosarcoma; Resistance.

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