Effect of EphA2 Silencing on Inhibiting the Progression of Renal Cell Carcinoma in an Orthotopic Mouse Model

Background: We investigated whether EphA2 inhibition can attenuate the progression of renal cell carcinoma (RCC) in an orthotopic mouse model of kidney tumor cells (Renca). Materials and Methods: 16 BALB/c mice were divided into two groups and implanted with either control or shRNA-mediated, EphA2-knockdown Renca-Luciferase cells via injection under the right renal capsule. Tumor progression was followed by in vivo bioluminescence imaging (BLI). Tumor growth was evaluated via ex vivo BLI and the wet weight of harvested orthotopic kidneys on day 18. Tumor apoptosis was evaluated using the TUNEL assay. Changes in FAK/RhoA signaling, a mediator of malignant cellular behavior, were determined using Western blotting and RT-PCR. Results: The TUNEL assay showed increased apoptosis of tumor cells in the EphA2-knockdown group compared to that in the control group (p = 0.021). Tumor wet weight (1569.9 ± 595.5 vs. 636.5 ± 288.9 mg, p = 0.009) and activation of RhoA and FAK were decreased in the EphA2-knockdown group (p < 0.05 for all). Tumor burden was reduced in the EphA2-knockdown group according to in vivo BLI on days 14 and 18 and an ex vivo test (p = 0.021, p = 0.043, p = 0.021). Conclusions: EphA2 knockdown significantly reduced the progression of RCC by inducing tumor apoptosis and suppressing FAK/RhoA signaling in an orthotopic mouse model. The EphA2/FAK/RhoA pathway might constitute a potential target to suppress the progression of RCC.