Radiosensitization of cancer cells by modulation of autophagy: Phosphoproteomic analysis

Ondrej, Martin

(ENG) Lung cancer, and in particular, non-small cell lung cancer (NSCLC), belongs to the most lethal oncological diseases worldwide. Choosing the proper therapeutic approach is, therefore, inevitable for the successful treatment of lung tumors. In this regard, radiotherapy is an essential therapeutic approach. However, like any other treatment option, radiotherapy has its limitations in the form of radioresistance. Autophagy has been generally accepted to be one of the most crucial factors in the radioresistance of tumor cells. It is, therefore, necessary to search for suitable approaches that would lead to the suppression of cytoprotective autophagy and, thus, to the radiosensitization of tumor cells. In this respect, in our study, we employed methods of quantitative phosphoproteomics along with several techniques of molecular biology to examine the underlying molecular mechanisms and signaling pathways involved in the regulation and inhibition of the autophagic process. To inhibit the cytoprotective autophagy, we used a relatively new autophagy inhibitor-Lys05, the analog of a well-described autophagy inhibitor chloroquine. As a model, we chose the radioresistant NSCLC cells (H1299; p53-negative), because they represent the most problematic group of cells within non-small cell lung tumors. The...

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