Surufatinib achieves radiosensitivity in cholangiocarcinoma by suppressing GINS4 expression to induce Ca2+/cAMP signaling activation

Figure 3 GINS4 is involved in the radiosensitizing effect of surufatinib on cholangiocarcinoma. A: A Venn diagram from RNA sequencing (RNA-seq) data identifies 23 genes associated with surufatinib (SF) and 6 Gy irradiation; B: Another Venn diagram highlights five genes differentially expressed in SF-induced radiosensitization; C: Heatmap analysis shows expression patterns of these genes across various treatment groups; D: RNA-seq analysis reveals significant downregulation of GINS4 following SF + 6 Gy treatment compared to radiotherapy or SF alone; E: Western blot confirms the changes in GINS4 expression across different groups; F and G: Analysis of GSE10072 and The Cancer Genome Atlas RNA-seq data indicates elevated GINS4 expression in tumors; H: High GINS4 expression correlates with poor prognosis; I: Western blot assesses GINS4 protein levels in NOZ and TFK-1 cells across four groups: Si-NC, si-NC + SF + 6 Gy, si-GINS4, si-GINS4 + SF + 6 Gy. Control (Ctrl) in panels J-L represents untreated control cells; si-NC served as the transfection control (data not shown separately due to similarity to Ctrl); J: Cell proliferation of NOZ and TFK-1 cells measured using the Cell Counting Kit-8 assay; K and L: Apoptosis rates determined by flow cytometry; M: Clonogenic survival rates evaluated using the clonogenic assay. All data are presented as mean ± SEM from three independent experiments. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001, ^dP < 0.0001. NS: Not significant; Ctrl: Control; SF: Surufatinib; RT: Radiotherapy; TCGA: The Cancer Genome Atlas.