Abstract
This study aimed to investigate the in vitro and in vivo antitumor effects and mechanisms of the small molecule anticancer drug CBL0137 in NK/T-cell lymphoma (NKTCL), as well as its efficacy when combined with chemotherapy or immunotherapy. Cell viability assays were performed to evaluate the inhibitory effect of CBL0137 on NKTCL cell proliferation in vitro. Flow cytometry was used to assess the effects of the drug on apoptosis and cell cycle progression. RNA sequencing (RNA-seq) was employed to explore the mechanism of action of CBL0137 in NKTCL, and Western blotting (WB) was used to validate the expression of related proteins. An in vivo xenograft model was used to confirm the antitumor activity of CBL0137. Additionally, immunohistochemistry analysis was conducted to further study tumor tissue. CBL0137 effectively inhibited the proliferation of NKTCL cells in vitro, induced apoptosis, and significantly blocked cell cycle progression. RNA-seq analysis revealed that CBL0137 exerts its antitumor effect primarily by interfering with DNA damage repair. In vivo experiments using xenografted mice confirmed the antitumor activity of CBL0137. CBL0137, when combined with PD-1 antibody, exhibits synergistic antitumor effects in mice, and its combination with cisplatin significantly enhances the sensitivity of NKTCL to cisplatin. CBL0137 inhibits DNA damage repair in NK/T-cell lymphoma and enhances its sensitivity to cisplatin.