Annexin A1 is involved in resistance to 5-FU in colon cancer cells

Abstract

Resistance to 5-fluorouracil (5‑FU), a key drug in the treatment of colorectal cancer, is one of the major reasons for poor patient prognosis during cancer treatment. Annexin A1 (ANXA1) is a calcium‑dependent phospholipid‑linked protein that is associated with drug resistance, anti‑inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. Although there have been several studies investigating ANXA1 expression in drug resistant cells, the role of ANXA1 is yet to be fully understood. We therefore, in this study, generated SW480 cells resistant to 5‑FU (SW480/5‑FU) to evaluate ANXA1 expression. When compared to the control cells, ANXA1 expression was significantly induced in the SW480/5‑FU cells. We then revealed the role of ANXA1 expression in 5‑FU resistance by using overexpression and knockdown methods in colon cancer cells. Overexpression of ANXA1 induced a significant increase of cell viability to 5‑FU, whereas ANXA1 knockdown induced a significant decrease of cell viability to 5‑FU. Further experiments revealed that ANXA1 expression was induced by hypoxia in colon cancer cells. These results suggest that ANXA1 expression may play a critical role in 5‑FU resistance and may be induced by hypoxia during cancer progression. Our results provide a possible strategy to overcome 5‑FU resistance by modulating ANXA1 expression.

DCST1-AS1 Promotes TGF-β-Induced Epithelial–Mesenchymal Transition and Enhances Chemoresistance in Triple-Negative Breast Cancer Cells via ANXA1

“…Jia et al found that knocking down ANXA1 enhanced the chemosensitivity of multiple myeloma cells to bortezomib (40). Onozawa et al found that overexpression of ANXA1 is associated with increased 5-FU resistance in colon cancer cells (41). Wang et al detected increased expression of ANXA1 mRNA and protein in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues (42).…”

iTRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma

“…We found 56 common differentially expressed proteins between the chemoresistant and the corresponding parent cell lines. Some proteins, such as HSPB1, 36,37 and ANXA1 38,39 have been reported on NPC or other cancers, whereas some proteins, such as PRDX1, STMN1, and TALDO1 were discovered in our study. Using iTRAQ labeling combined with NanoLC-MS/MS, we identified a spectrum of CDDP resistance-associated proteins in NPC cell lines that provides insights into the resistance mechanism of cancer cells.…”

“…In addition, the differential expression of ANXA1 and TRIM29 were confirmed further with PCR and western blotting, because our previous study showed that overexpression of this protein could promote invasion and metastasis of NPC. 39,67 The tripartite motif (TRIM) family characterized by a series of conserved domains, including a Ring-finger domain, one or two B-box zinc-finger motifs, and a coiledcoil domain, comprises multi-domain ubiquitin E3 ligases. Thus far, some of the TRIM family proteins are reported to regulate important cellular processes such as cell proliferation, migration, invasion, and carcinogenesis.…”

Annexin A1 is upregulated in p53-positive gastric cancer

“…The colon cancer cases with positive ANXA1 staining were not statistically associated with poor survival 5) . However, our recent findings suggested that upregulated ANXA1 expression may play a critical role in 5-FU resistance in colon cancer cells, indicating the association between ANXA1 and worsened colon cancer outcome 6) . In gastric cancer, ANXA1 is also thought to play a critical role in cancer development 7,8) .…”

“…IHC staining was performed as previously described 6,11) . Briefly, gastric cancer cells were fixed in 10% formalin and embedded in paraffin, then cut into 4 μm sections and stained.…”