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.

中文翻译：

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不同水平Ppm1d表达的细胞对经典化疗药物对大肠癌治疗的敏感性

摘要

已经在各种肿瘤中发现了编码Wip1磷酸酶的Ppm1d基因的突变和扩增。最近的研究表明，化疗后Wip1稳定突变体的存在表明Wip1参与了恶性细胞对化疗药物的耐药性。在目前的工作中，我们调查了Wip1在结肠癌细胞对抗肿瘤药物5-氟尿嘧啶和奥沙利铂的反应中的作用。使用慢病毒转导获得获得具有增加的Ppm1d表达水平的细胞系。已经显示，Wip1过表达可维持暴露于奥沙利铂的细胞的细胞活力，同时删除Ppm1d在这些药物的联合和单次接触下，该基因都会降低生存力和克隆形成能力。这些发现表明，化疗期间癌细胞中Wip1水平的升高可能有助于癌细胞对抗肿瘤治疗的耐药性的发展。旨在降低Wip1水平的方法将提高结肠癌治疗的效率。