Pancreatic ductal adenocarcinoma (PDAC) has a poor response to the first-line chemotherapy drug gemcitabine. We previously identified stanniocalcin-1 as a gemcitabine-resistant-related gene, but its specific role and function in pancreatic cancer remain unclear. RT-qPCR and Western blot were used to evaluate differential protein and mRNA expressions. The biological functions of genes were determined using proliferation and drug-resistance experiments. Subcutaneous tumorigenesis experiment was performed on nude mice. Prognostic analysis was performed using public databases and our clinical data. We found HIF-1α-regulated STC1 expression mediated chemoresistance in pancreatic cancer. Deeper, we explored the action mechanism of STC1 and identified PI3K/AKT as the downstream signaling pathway of STC1. Furthermore, we analyzed clinical data and found that STC1 expression was related to the prognosis of gemcitabine-treated patients after surgery. In general, we proved the HIF-1α/STC1/PI3K-AKT axis participated in PDAC progression and chemoresistance, and STC1 may serve as a potential prognostic factor and therapeutic target for PDAC treatment.

中文翻译：

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HIF-1α 调节的 stanniocalcin-1 通过 PI3K/AKT 信号通路介导胰腺导管腺癌对吉西他滨的耐药性

胰腺导管腺癌 (PDAC) 对一线化疗药物吉西他滨的反应较差。我们之前将 stanniocalcin-1 鉴定为吉西他滨耐药相关基因，但其在胰腺癌中的具体作用和功能仍不清楚。RT-qPCR和Western印迹用于评估差异蛋白和mRNA表达。使用增殖和抗药性实验确定基因的生物学功能。对裸鼠进行皮下成瘤实验。使用公共数据库和我们的临床数据进行预后分析。我们发现 HIF-1α 调节的 STC1 表达介导了胰腺癌的化学抗性。更深入地，我们探索了STC1的作用机制，并将PI3K/AKT确定为STC1的下游信号通路。此外，我们分析了临床数据，发现STC1的表达与吉西他滨治疗的患者术后预后有关。总的来说，我们证明了 HIF-1α/STC1/PI3K-AKT 轴参与了 PDAC 进展和化疗耐药，STC1 可能作为 PDAC 治疗的潜在预后因素和治疗靶点。