Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin

• DOI: 10.1186/s12964-017-0164-3
• Publication Date: 2017-02-01T03:04:05Z
• Authors: Ulrich-Axel Bommer; Kara L. Vine; Prianka Puri; Martin Engel; Lisa Belfiore; Karen Fildes; Marijka Batterham; Alistair Lochhead; Morteza Aghmesheh
• Keywords: 0301 basic medicine; Cell Death; Organoplatinum Compounds; Carcinogenesis; Research; TOR Serine-Threonine Kinases; Tumor Protein, Translationally-Controlled 1; Cell Biology; Mechanistic Target of Rapamycin Complex 1; HCT116 Cells; 3. Good health; Gene Expression Regulation, Neoplastic; Oxaliplatin; 03 medical and health sciences; Drug Resistance, Neoplasm; Multiprotein Complexes; Medicine and Health Sciences; Biomarkers, Tumor; Humans; Fluorouracil; RNA, Messenger; Colorectal Neoplasms; Molecular Biology; Signal Transduction

Translationally controlled tumour protein TCTP is an anti-apoptotic frequently overexpressed in cancers, where high levels are often associated with poor patient outcome. may be involved protecting cancer cells against the cytotoxic action of anti-cancer drugs. Here we study early increase human colorectal (CRC) and regulation expression HCT116 colon cells, response to treatment drugs 5-FU oxaliplatin.Using immunohistochemistry, assessed surgical samples from adenomas adenocarcinomas colon, compared normal tissue. We also studied oxaliplatin by western blotting. mRNA were RT-qPCR. used mTOR kinase inhibitors demonstrate mTOR-dependent translational under these conditions. Employing Real-Time Cell Analysis (RTCA) System MTS assay, investigated effect TCTP-knockdown on sensitivity oxaliplatin.1. significantly increased adenocarcinomas, 2. about 4-fold upregulated treatment, whereas down regulated. 3. prevented up-regulation protein, indicating that translationally regulated through complex 1 signalling pathway 4. Using two cellular assay systems, demonstrated sensitises cytotoxicity caused oxaliplatin.Our results stages CRC development. In this largely during DNA-damaging oxaliplatin, as part stress response. thus contribute development drug resistance. These findings indicate might suitable a biomarker combinatorial using 5-FU/oxaliplatin, together inhibitors, could route preventing resistance