China Oncology ›› 2020, Vol. 30 ›› Issue (9): 682-688.doi: 10.19401/j.cnki.1007-3639.2020.09.007

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Expression of O-GlcNAc transferase in osteosarcoma and its effect on proliferation and sensitivity to cisplatin

ZHU Kaizhong, WANG Tingrui, CHEN Huanxiong, CHEN Tao, ZHONG Zhenhao   

  1. Department of Spinal Osteopathy Surgery, the First Affiliated Hospital of Hainan Medical College, Haikou 570102, Hainan Province, China
  • Online:2020-09-30 Published:2020-10-12
  • Contact: ZHONG Zhenhao E-mail: 2499264010@qq.com

Abstract: Background and purpose: O-GlcNAc transferase (OGT) is widely involved in biological behaviors of tumor cells and associated with tumor progression. In this study, we measured expression level of OGT in osteosarcoma tissues, and evaluated its effect on proliferation of the osteosarcoma cells and their sensitivity to cisplatin. Methods: OGT expression was determined by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), Western blot and immunohistochemistry, and its effects on clinicopathological features and prognosis of the patients who were treated in the First Affiliated Hospital of Hainan Medical College were evaluated. Then, OGT expression in osteosarcoma cells was silenced by RNA interference to detect its effect on cell proliferation, as demonstrated by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2’-deoxyuridine (EdU) assay. And mRNA and protein expressions of OGT in the osteosarcoma cells were also observed after treatment with cisplatin. Furthermore, the osteosarcoma cells were treated with cisplatin after modulation of OGT expression to measure its effect on cisplatin sensitivity of the osteosarcoma cells, as depicted by CCK-8 assay and apoptosis assay using flow cytometry. Results: The results of RTFQ-PCR, Western blot and immunohistochemistry demonstrated that a significant increase in OGT expression in osteosarcoma tissues (P<0.05), which was closely related to larger size of tumor, more advanced pathological stage and poorer prognosis (P<0.05). After silencing OGT, proliferation of the osteosarcoma cells significantly decreased (P<0.05). And OGT expression increased in response to cisplatin treatment in a dose-dependent manner. Silencing OGT in osteosarcoma cells significantly enhanced their sensitivity to cisplatin (P<0.05), while overexpressing OGT led to cisplatin tolerance. Conclusion: OGT is highly expressed in osteosarcoma tissues and closely related to prognosis of the patients. Silencing OGT expression can inhibit growth of osteosarcoma and sensitize it to cisplatin. OGT may be a potential biomarker for targeted therapy of osteosarcoma.

Key words: O-GlcNAc transferase, Proliferation, Cisplatin, Osteosarcoma