CS2164 combined with radiation impaired tumor growth by interfering with DNA damage repair and modifying tumor environment

CS2164 is an oral anti-tumor inhibitor that targets angiogenesis-related kinases, mitosis-related kinases, and chronic inflammation-related kinases. However, the added clinical benefit of CS2164 combined with radiation remains unknown. The hepatocellular carcinoma and cervical cancer cell lines were selected to evaluate the anti-tumor effect of CS2164 combined with radiation using cell growth and colony formation assays. Further, xenograft radiation models were constructed to evaluate in vivo effects. Finally, transcriptome sequencing and bioinformatics analysis were performed to elucidate the mechanisms. In this study, we found that CS2164 combined with radiation significantly decreased growth of tumors in vitro and in vivo. The γ-H2AX immunofluorescence staining results indicated that CS2164 enhanced radiation-induced DNA double strand breaks (DSBs) and suppressed the DNA damage repair process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis screened out a series of pathways that related to cell death types and immune tolerances, in the CS2164 plus radiation group compared with the control group. Meanwhile, protein-protein interaction regulator network was used to determine the core regulatory molecules landscape, including DNA damage repair process, microtubule formation, calcium channels, etc.