Annexin A1 is involved in resistance to 5-FU in colon cancer cells
Annexin A1 is involved in resistance to 5-FU in colon cancer cells
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DOI：
10.3892/or.2016.5234
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发表时间：
2017-01-01
期刊：
影响因子：
4.2
通讯作者：
Takenoshita, Seiichi
中科院分区：
文献类型：
--
作者：
Onozawa, Hisashi;Saito, Motonobu;Takenoshita, Seiichi
5-氟尿嘧啶（5-FU）是治疗结直肠癌的关键药物，耐药是癌症治疗中患者预后差的主要原因之一。膜联蛋白A1 （ANXA1）是一种钙依赖性磷脂连接蛋白，与耐药、抗炎作用、细胞分化、增殖和凋亡调节有关。虽然已经有一些研究调查了耐药细胞中ANXA1的表达，但ANXA1的作用尚未完全了解。因此，在本研究中，我们生成了耐5-FU的SW480细胞（SW480/5-FU）来评估ANXA1的表达。与对照细胞相比，SW480/5-FU细胞显著诱导ANXA1表达。然后，我们通过结肠癌细胞的过表达和敲低方法揭示了ANXA1表达在5-FU耐药中的作用。过表达ANXA1诱导细胞对5-FU的活力显著增加，而敲低ANXA1诱导细胞对5-FU的活力显著降低。进一步实验发现，缺氧可诱导结肠癌细胞中ANXA1的表达。这些结果表明，ANXA1的表达可能在5-FU抵抗中起关键作用，并可能在癌症进展过程中由缺氧诱导。我们的研究结果提供了一种通过调节ANXA1表达来克服5-FU耐药性的可能策略。
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.