Fig. 6

CCHE1 desensitized melanoma cells to dacarbazine via glycolysis. A CCHE1 expression was significantly increased in dacarbazine-resistant melanoma cells. B Dacarbazine resistant A375 (A375R) and G-361 (G-361R) cells were transfected with siRNA-control or siRNA-CCHE1. Cells were treated with dacarbazine for 48 h and the cell viability was determined by CCK-8 assay. C, D Cells were treated with 100 μg/ml dacarbazine for 48 h, and CCHE1 overexpression significantly reversed dacarbazine-induced cell death. E The expression of CCHE1 in dacarbazine resistant melanoma patients was significantly higher than patients sensitive to dacarbazine. F In vivo xenograft mouse model was established by transplanting A375 cells transfected with lentivirus expressing control vector or CCHE1. Mice were treated with dacarbazine and the tumor volume of the CCHE1 group was significantly increased compared with the control after dacarbazine exposure. Overexpression of CCHE1 in the xenograft tumors was validated at the endpoint. Representative tumors were shown. G, H Transfection of CCHE1 significantly reduced the sensitivity of melanoma cells to cisplatin treatment. I, J Melanoma cells were treated with dacarbazine and overexpression of CCHE1 increased the cell viability. Addition of 2-DG attenuated the function of CCHE1 in desensitized melanoma cells to dacarbazine. *p < 0.05, **p < 0.01, ***p < 0.001