Abstract
BackgroundChemoresistance is a major obstacle to successful chemotherapy for colorectal cancer. Eukaryotic translation initiation factor 5A2 (eIF5A2), one of the two isoforms in the eIF5A family, has been reported to be a new oncogene in many types of human cancer. In the present study, we aimed to investigate whether eIF5A2 was involved in the chemoresistance to doxorubicin in colorectal cancer.MethodsCell viability was measured by CCK-8 assay with or without doxorubicin treatment. Protein expression was detected by western blot. Tumor cells were transfected with eIF5A2 siRNA or plasmid encoding eIF5A2 to down- or up regulate the expression of eIF5A2.ResultsWe found that eIF5A2-negtive colon cancer cells (HCT116 and HT29) were more sensitive to doxorubicin compare with the eIF5A2-positive cells (LOVO and SW480). Downregulation of eIF5A2 in LOVO and SW480 cells enhanced the chemosensitivity to doxorubicin. On the contrary, overexpression of eIF5A2 reduced doxorubicin sensitivity in colon cancer cells. In addition, eIF5A2 knockdown increased the protein level of E-cadherin and reduced vimentin expression in LOVO and SW480 cells. Meanwhile, upregulation of eIF5A2 potentiated epithelial mesenchymal transition (EMT) in colon cancer cells. Moreover, blockade of EMT with Twist siRNA abolished eIF5A2-regulated chemoresistance in colon cancer cells.ConclusionOur present study demonstrated that eIF5A2 promoted the chemoresistance to doxorubicin via regulation of EMT in colon cancer cells. Therefore, eIF5A2 inhibition may be a new potential strategy for the reversal of drug resistance in colorectal cancer therapy.
Highlights
Chemoresistance is a major obstacle to successful chemotherapy for colorectal cancer
Different doxorubicin sensitivity in colon cancer cells Firstly, CCK-8 assay was performed to measure the sensitivity of different colon cancer cell lines (HCT116, HT29, LOVO and SW480) to doxorubicin
SW480 cells were more sensitive to doxorubicin compared with LOVO cells (Fig. 1b)
Summary
Chemoresistance is a major obstacle to successful chemotherapy for colorectal cancer. We aimed to investigate whether eIF5A2 was involved in the chemoresistance to doxorubicin in colorectal cancer. Emerging evidence suggests that EMT plays a critical role in the regulation of chemoresistance properties of cancer cells [15, 16]. Eukaryotic translation initiation factor 5A2 (eIF5A2) mainly acts as an elongation factor during mRNA translation step. It has been identified as an oncogene in ovarian cancer, suggesting that aberrant expression of eIF5A2 may be responsible for the malignant behavior of cancer cells [17,18,19]. The present study aimed to investigate the biological role of eIF5A2 in colorectal cancer chemoresistance
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