Suppression of the Expression of Molecular Chaperones as a Factor in Increasing the Efficiency of Antitumor Therapy

Modern methods of antitumor chemotherapy are not able to destroy 100% of the cell population. The use of modern methods of chemotherapy is constrained by the increased efficiency of cancer cells’ cellular-defense systems, in particular, molecular chaperones, the expression of which increases with the use of anticancer drugs. Combination therapy with inhibitors of individual chaperones, in particular, Hsp70, or HSF1, which regulates the synthesis of heat-shock proteins, can be a means to increase the effectiveness of anticancer drugs. In the present study, we compared the effect of increasing the sensitivity of A549 lung adenocarcinoma cells with the suppression of Hsp70 or HSF1 activity in tumor cells. Having obtained the A549-shHsp70 and A549-shHSF1 sublines using the RNA interference method, we compared their sensitivity to the action of the anticancer drugs etoposide and oxaliplatin. Suppression of the function of Hsp70 and decrease in HSF1 activity increased the number of dead cells and increased the activity of caspase-3/7, and the effect of HSF1 inactivation significantly exceeded the results of Hsp70 inhibition. We can conclude that HSF1 inhibitors have therapeutic potential as a part of antitumor compositions.