PARP inhibitor exerts an anti-tumor effect via LMO2 and synergizes with cisplatin in natural killer/T cell lymphoma

BMC Medicine

Research Article

Shuo Huang¹  Jiazhuo Wu²  Cunzhen Shi²  Wenting Song²  Jianxiang Zhang²  Mingzhi Zhang²  Hongwen Li²  Zhaoming Li²  Wencai Li³ 

[1] Department of Infectious Diseases and Hepatology, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;Department of Pathology, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;

关键词: PARP inhibitor;    LMO2;    Natural killer/T cell lymphoma;    DNA damage repair;   

DOI  :  10.1186/s12916-023-02904-9

 received in 2022-12-04, accepted in 2023-05-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPARP inhibitor (PARPi), as a kind of DNA damage repair inhibitor, has been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we investigated the efficacy and mechanism of PARPi, and the therapeutic value of PARPi combined with cisplatin in NKTCL.MethodsThe cell proliferation, cell apoptosis, and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-sequencing, quantitative real-time PCR, western blotting, and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo.ResultsPARPi inhibited cell proliferation, promoted cell apoptosis, and induced S-phase cell cycle arrest in NKTCL cells. PARPi led to the accumulation of DNA damage by blocking DNA repair and DNA replication. Additionally, LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPi. Finally, the combination of PARPi and cisplatin exhibited significant synergistic effects both in vitro and in vivo.ConclusionsIn summary, we found that PARPi exerted an anti-tumor effect via LMO2 and synergized with cisplatin in NKTCL, which provides the theoretical basis for the clinical application of PARPi.

【 授权许可】

CC BY   
© The Author(s) 2023

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