Sensitivity of Cells with Various Levels of Ppm1d Expression to Classical Chemotherapeutic Drugs for Colorectal Cancer Treatment

Abstract

Mutations and amplifications of the Ppm1d gene encoding Wip1 phosphatase have been found in various tumors. Recent studies have shown that the presence of Wip1 stable mutant after chemotherapy suggests that Wip1 is involved in the resistance of malignant cells to chemotherapeutic drugs. In the present work, we investigated the role of Wip1 in the response of colon cancer cells to the antitumor drugs 5-fluorouracil and oxaliplatin. Cell lines with an increased level of Ppm1d expression were obtained with acquired using lentiviral transduction. It has been shown that Wip1 overexpression maintains the cell viability of cells exposed to oxaliplatinum, while deletion of the Ppm1d gene decreases the viability and clonogenicity both under the combined and single exposure to these drugs. These findings suggest that an increased Wip1 level in cancer cells during chemotherapy may contribute to the development of cancer cell resistance to antitumor therapy. Methods aimed at reducing the Wip1 level will increase the efficiency of colon cancer treatment.