Hypoxia-related proteins VEGF A and CA IX and resistance of soft tissue sarcoma cells to chemotherapy: <i>ex vivo</i> pilot study

Abstract

Introduction. The identification of predictive factors is a cornerstone task of modern oncology. The development of new targeted drugs determines the need for prediction of chemosensitivity of each patient to the prescribed therapy, in this regard, the search for biomarkers of predictive response to therapy is actively conducted.The study objective to investigate the relationship between tumor cell resistance and the expression levels of CA IX (carbonic anhydrase IX) and VEGF A (vascular endothelial growth factor А) in patient-derived cultures of soft tissue sarcomas.Materials and methods: ex vivo soft tissue sarcoma cell culture, resazurin test, immunoblotting.Results. We obtained 46 ex vivo samples of soft tissue sarcoma cultures for which chemosensitivity to doxorubicin, ifosfamide, docetaxel, gemcitabine, and their combinations was assessed by the resazurin cytotoxicity test. We analyzed the relationship between the expression of hypoxic proteins VEGF A and CA IX and the resistance to drugs. A correlation between the CA IX expression in hypoxia and cell resistance to ifosfamide and its combination with doxorubicin was found. Soft tissue sarcomas with high VEGF A index were resistant to doxorubicin, docetaxel, and its combination with gemcitabine (p <0.05).Conclusion. The data obtained on patient-derived cultures indicate the relationship between hypoxic signaling and resistance of soft tissue sarcomas to chemotherapeutics.

Keywords

• soft tissue sarcoma
• signaling pathways
• targeted chemotherapy
• prediction of individual sensitivity and development of drug resistance
• vegf a
• ca ix