Reduced Lipocalin 2 Expression Contributes to Vincristine Resistance in Human Colon Cancer Cells.

Abstract

Vincristine (VCR) resistance can lead to cancer chemotherapy failure. Although changes in gene expression are responsible for drug resistance, the specific identities and roles of these genes remain unclear. In this study, we aimed to identify differentially expressed genes and mechanisms of VCR resistance in colorectal cancer (CRC) cells. A VCR-resistant CRC cell line (HCT-8/VCR) was established, and differentially expressed proteins between HCT-8 and HCT-8/VCR cells were screened using a human cytokine array; the results were confirmed by reverse transcription polymerase chain reaction and Western blotting. Furthermore, differentially expressed proteins were downregulated using siRNA, and cell proliferation and apoptosis were assessed by Cell Counting Kit-8 assay and flow cytometry, respectively. Compared with HCT-8 CRC cells, HCT-8/VCR cells showed downregulation of lipocalin 2 (LCN2). We found that siRNA-mediated downregulation of LCN2 in HCT-8 cells significantly increased VCR resistance. Furthermore, when we downregulated LCN2, we observed significant decreases in apoptosis, but no significant effect on cell cycle. Overall, these results demonstrate that LCN2 plays an important role in VCR resistance and is a potential therapeutic target for this disease.