RADIATION-DEPENDENT CHANGES IN THE EXPRESSION OF HEDGEHOG SIGNALING PATHWAY GENES IN PDX MODELS OF SQUAMOUS CELL CANCER CARCINOMA OF THE ESOPHAGUS
Esophageal cancer is one of the most common cancers with a poor prognosis. The main treatment strategies, radiation therapy combined with surgery, are still not effective enough and require further optimization. Targeted therapy aimed at regulating key signaling pathways has the potential to increase the effectiveness of treatment for esophageal cancer. Our study is devoted to the search for the choice of the optimal radiation dose and the search for target genes of the Hedgehog signaling pathway, which could form the basis of targeted therapy and increase the effectiveness of radiation treatment for squamous cell carcinoma of the esophagus. The object of the study was mouse orthotopic models of esophageal cancer, divided into five groups depending on the received single dose of radiation: 0 Gy, 4 Gy, 6 Gy, 8 Gy and 10 Gy, respectively. After the application of the radiation dose, the expression of the genes of the Hedgehog signaling pathway in the tumor tissue was determined: SHH, IHH, PTCH1, PTCH2 GLI1, and SMO. According to the results of the study, the optimal radiation dose was 6 Gy; in the corresponding group, inhibition of tumor growth by 88.4% was observed. The use of radiation doses led to an increase in the expression level of SHH, IHH, and GLI1 of the Hedgehog signaling pathway in all studied groups. Our results confirm the need for further research using SHH, IHH and GLI1 inhibitors. The selected optimal dose of radiation in combination with inhibitors of SHH, IHH and GLI1 can significantly increase the effectiveness of treatment of squamous cell carcinoma of the esophagus, preventing tumor growth and reducing the risk of metastasis.