DNA‐binding protein A (dbpA) is reported to be upregulated in many cancers and associated with tumor progress. The present study aimed to investigate the role of dbpA in 5‐fluorouracil (5‐FU)‐resistant and oxaliplatin (L‐OHP)‐resistant colorectal cancer (CRC) cells. We found that 5‐FU and L‐OPH treatment promoted the expression of dbpA. Enhanced dbpA promoted the drug resistance of SW620 cells to 5‐FU and L‐OHP. DbpA knockdown inhibited cell proliferation, induced cell apoptosis, and cell cycle arrested in SW620/5‐FU and SW620/L‐OHP cells. Besides, dbpA short hairpin RNA (shRNA) enhanced the cytotoxicity of 5‐FU and L‐OHP to SW620/5‐FU and SW620/L‐OHP cells. Meanwhile, dbpA shRNA inhibited the activation of the Wnt/β‐catenin pathway that induced by 5‐FU stimulation in SW620/5‐FU cells. Activation of the Wnt/β‐catenin pathway or overexpression of checkpoint kinase 1 (Chk1) abrogated the promoting effect of dbpA downregulation on 5‐FU sensitivity of CRC cells. Importantly, downregulation of dbpA suppressed tumor growth and promoted CRC cells sensitivity to 5‐FU in vivo. Our study indicated that the knockdown of dbpA enhanced the sensitivity of CRC cells to 5‐FU via Wnt/β‐catenin/Chk1 pathway, and DbpA may be a potential therapeutic target to sensitize drug resistance CRC to 5‐FU and L‐OHP.

中文翻译：

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敲低 DNA 结合蛋白 A (dbpA) 通过抑制 Wnt/β-catenin/Chk1 通路增强结直肠癌的化疗敏感性。

据报道，DNA 结合蛋白 A (dbpA) 在许多癌症中上调并与肿瘤进展相关。本研究旨在研究 dbpA 在 5-氟尿嘧啶 (5-FU) 耐药和奥沙利铂 (L-OHP) 耐药的结直肠癌 (CRC) 细胞中的作用。我们发现 5-FU 和 L-OPH 处理促进了 dbpA 的表达。增强的 dbpA 促进了 SW620 细胞对 5-FU 和 L-OHP 的耐药性。DbpA 敲低抑制了 SW620/5-FU 和 SW620/L-OHP 细胞中的细胞增殖、诱导细胞凋亡和细胞周期停滞。此外，dbpA 短发夹 RNA (shRNA) 增强了 5-FU 和 L-OHP 对 SW620/5-FU 和 SW620/L-OHP 细胞的细胞毒性。同时，dbpA shRNA 抑制了 SW620/5-FU 细胞中由 5-FU 刺激诱导的 Wnt/β-catenin 通路的激活。Wnt/β-catenin 通路的激活或检查点激酶 1 (Chk1) 的过表达消除了 dbpA 下调对 CRC 细胞 5-FU 敏感性的促进作用。重要的是，dbpA 的下调抑制了肿瘤生长并促进了体内 CRC 细胞对 5-FU 的敏感性。我们的研究表明，dbpA 的敲低通过 Wnt/β-catenin/Chk1 通路增强了 CRC 细胞对 5-FU 的敏感性，并且 DbpA 可能是使耐药性 CRC 对 5-FU 和 L-OHP 敏感的潜在治疗靶点。