Effect of Targeted Therapy With Pazopanib on Expression Levels of Transcription, Growth Factors and Components of AKT/m-TOR Signaling Pathway in Patients with Renal Cell Carcinoma

Document Type: Research Articles

Authors

1 Cancer Research Institute, Tomsk National Research Center, Russian Academy of Medical Sciences, Tomsk, Russia.

2 Siberian State Medical University, Tomsk, Russia.

Abstract

 
Background: The effect of the targeted therapy on cancer molecular markers remains currently unknown. The aim of the study was to investigate the expression and content of transcription, growth factors and components of the AKT/m-TOR signaling pathway in kidney cancer patients before and after targeted therapy with pazopanib. Methods: A total of 157 patients with renal cell carcinoma were enrolled into the study. The level of mRNA expression was investigated by real-time PCR, and the contents of transcription and growth factors, as well as the levels of AKT/m- TOR signaling pathway components were determined by ELISA and Western blotting. Results: Targeted therapy with pazopanib resulted in a 3.1-fold decrease in HIF-2α expression that was accompanied by a reduction in the levels of NF-κB p65 and p50, HIF-1α and CAIX. The levels of GSK-3ß and AKT mRNA were increased; however, the levels of corresponding proteins remained low. The targeted therapy with pazopanib did not influence the level of PTEN phosphatase. A 1.9-fold increase in the level of p70 S6 (S371) was observed after therapy. Conclusion: The efficacy of tyrosine kinase inhibitors is associated with the changes in the angiogenic factors. Molecular characteristics of cancer could determine markers of disease progression as well as potential targets for anticancer therapies

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