肿瘤干细胞与胰腺癌的化疗耐药密切相关。我们在前期研究中发现，胰腺癌细胞高表达干性转录因子Sox8。它参与了肿瘤细胞干性特征的维持，并与吉西他滨的耐药有关。然而，在以乏氧为特征的胰腺癌微环境下，Sox8的表达调控模式及其影响细胞干性与化疗耐药的分子机制仍需进一步探讨。本课题在前期工作基础上，拟从临床水平、细胞水平以及动物水平分别分析Sox8表达水平与早期患者术后复发，及晚期患者化疗耐药的相关性；揭示Sox8促进胰腺癌细胞干性及化疗耐药的分子机制，阐明胰腺癌特征性乏氧微环境影响Sox8表达与功能的分子基础和调控方式，并利用裸鼠移植瘤和PDX (Patient-derived Xenograft)模型深入讨论HIF-1α/Sox8通路对胰腺癌肿瘤干细胞及化疗耐药的影响及其作用机制。针对Sox8功能及表达机制的研究将丰富我们对胰腺癌干细胞的认知，为逆转胰腺癌耐药提供新的思路。

Cancer stem cells are closely associated with chemotherapy resistance in pancreatic cancer. In the previous study, we discovered that stem cell transcription factor, Sox8, is highly expressed in pancreatic cancer, and participated in the promotion of stemness maintenance and gemcitabine resistance. However, the mechanism of Sox8 expression and function still remains to be elucidated, especially under the characteristic hypoxia microenvironment of pancreatic cancer. Based on our previous results, we aim to explore the expression and function of Sox8 from clinical level, cellular level and animal model level, to analyze its correlation with relapse rate in patients of early stages and chemo-resistance rate in patients of late stages, to elucidate the mechanism of Sox8 on stemness maintenance and chemo-resistance, and also its expression under hypoxia microenvironment. We also use nude mice and patient-derived xenograft model to further discuss the function and mechanism of HIF-1α/Sox8 pathway on stemness maintenance and chemo-resistance. In conclusion, the study of the function and regulatory mechanism of Sox8 in pancreatic cancer would expect to understand more on cancer stem cell, and provide novel mechanism for chemotherapy resistance.