Wei Qu, Yufei Wang, Qining Wu, Dingjun Hao, Dichen Li
(Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, China (mainland))
Med Sci Monit 2017; 23:5767-5773
This study aimed to investigate the possible involvement of sonic hedgehog (Shh) signaling in the radioresistance of human osteosarcoma cells and the inhibitory effects of emodin on radioresistance.
MATERIAL AND METHODS: Human osteosarcoma (OS) cell line MG63 was employed as parent cells. After 30-repeat low-dose (2 Gy) x-ray irradiation on MG63 cells, radioresistant OS cell MG63R cells were produced. Colony formation assay was used to assess the radioresistance. Cell viability was evaluated by CCK-8 assay. TUNEL assay was used to detect cell apoptosis. Protein expression levels and nuclear translocation were evaluated by western blotting.
RESULTS: More survival colony formation, elevated cell viability, and less cell apoptosis were found in MG63R cells compared to MG63 cells exposed to irradiation. The nuclear translocation of glioma-associated oncogene homolog (Gli), expression levels of Shh and Bcl2 were increased in MG63R cells compared to MG63 cells. Emodin pretreatment significantly inhibited cell viability and survival colony formation but increased cell apoptosis of irradiation exposed MG63R cells in a concentration dependent manner. Moreover, emodin pretreatment inhibited Shh and Bcl2 expressions as well as Gli1 nuclear translocation but increased C-caspase-3 expression of irradiation exposed MG63R cells in a concentration dependent manner.
CONCLUSIONS: Shh signaling activation was involved in the radioresistance of human OS cells. Emodin impaired the radioresistant capacity of OS cells by inhibiting Shh signaling pathway.
Keywords: Emodin, Osteosarcoma, Radiotherapy, Adjuvant