Synergistic antitumor effect of oroxylin A and donafenib in hepatocellular carcinoma through tumor protein p53 signaling pathway activation

Figure 3 Synergistic activation of the TP53 signaling pathway by oroxylin A and donafenib in hepatocellular carcinoma cells. A and B: The mRNA expression of tumor protein p53, murine double minute 2 (MDM2), MDM4, cyclin-dependent kinase 9, B-rapidly accelerated fibrosarcoma proto-oncogene serine/threonine kinase, vascular endothelial growth factor receptor, and cell division cycle 7 in MHCC-97H (A) and PLC-PRF-5 (B) cells was measured using quantitative real-time polymerase chain reaction after treatment with oroxylin A and/or donafenib; C: The protein levels of tumor protein p53, MDM2, MDM4, phosphorylated MDM2, phosphorylated MDM4, cyclin-dependent kinase 9, and B-rapidly accelerated fibrosarcoma proto-oncogene serine/threonine kinase, vascular endothelial growth factor receptor, and cell division cycle 7 were examined using Western blot analysis in both cell lines following treatment with oroxylin A and/or donafenib. Data are presented as mean ± SD. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001, ^dP < 0.0001, ns: P > 0.05. DMSO: Dimethyl Sulfoxide; OA: Oroxylin A; DF: Donafenib; OA + DF: Oroxylin A + donafenib; MDM2: Murine double minute 2; MDM4: Murine double minute 4; CDK9: Cyclin-dependent kinase 9; TP53: Tumor protein p53; CDC7: Cell division cycle 7; BRAF: B-rapidly accelerated fibrosarcoma proto-oncogene serine/threonine kinase; VEGFR: Vascular endothelial growth factor receptor; p-MDM2: Phosphorylated murine double minute 2; p-MDM4: Phosphorylated murine double minute 4.