Background: 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.
Objective: In this study, we aimed to identify differentially expressed genes and mechanisms of VCR
resistance in colorectal cancer (CRC) cells.
Methods: 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.
Results: 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.
Conclusion: Overall, these results demonstrate that LCN2 plays an important role in VCR resistance
and is a potential therapeutic target for this disease.