非小细胞肺癌患者血浆可溶性TRAIL对循环ALDH1+肿瘤干细胞样细胞的影响及其机制研究

项目名称： 非小细胞肺癌患者血浆可溶性TRAIL对循环ALDH1+肿瘤干细胞样细胞的影响及其机制研究

项目编号： No.81502558

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 夏蒲

作者单位： 锦州医科大学

项目金额： 18万元

中文摘要： 肺癌已成为我国发病率和死亡率最高的恶性肿瘤。肿瘤干细胞样细胞在非小细胞肺癌的发生和治疗过程中起关键作用，但循环肿瘤干细胞样细胞对非小细胞肺癌患者疗效和预后的影响尚不明确。我们前期工作成功地从非小细胞肺癌患者外周血中分离乙醛脱氢酶1 (ALDH1)阳性的循环肿瘤细胞，进一步研究发现可溶性肿瘤坏死因子相关的凋亡诱导配体(sTRAIL)含量与ALDH1+肿瘤细胞数量呈负相关，MTT实验显示sTRAIL能够抑制ALDH1+肿瘤细胞增殖。由此我们提出sTRAIL可能应用于肺癌ALDH1+肿瘤干细胞样细胞治疗这一科学命题。在本项目中，我们将利用细胞实验和裸鼠荷瘤模型进行sTRAIL对ALDH1+肿瘤细胞作用的研究，探索sTRAIL和ALDH1+肿瘤细胞作为非小细胞肺癌患者疗效和预后标志物的可行性。本研究对阐明sTRAIL抑制肿瘤干细胞的分子机制具有重要意义。

中文关键词： 肿瘤干细胞；乙醛脱氢酶1；可溶性肿瘤坏死因子相关的凋亡诱导配体；非小细胞肺癌；凋亡

英文摘要： Lung cancer has become the highest malignant tumor incidence and mortality in China. Cancer stem cells-like cell plays a key role in the tumorigenesis and therapy of non small cell lung cancer (NSCLC). However, the roles of circulating cancer stem cells-like cell in the curative effect and prognosis of the patients with NSCLC remain unclear. Our previous work has successfully isolated aldehyde dehydrogenase 1 (ALDH1) positive circulating cancer cells from the peripheral blood of the patients with NSCLC. Furthermore, we found that the content of sTRAIL (soluble tumor necrosis factor-related apoptosis-inducing ligand, sTRAIL) was negatively correlated with the number of ALDH1+ tumor cells. And the result of MTT assay showed that sTRAIL could inhibit the proliferation of ALDH1+ tumor cells. Based on these findings, we hypothesized that sTRAIL may be applied in the treatment of ALDH1+ cancer stem cells-like cell. We will detect the roles of sTRAIL in ALDH1+ tumor cell by using cell experiments and nude mouse model, and explore the possibility of sTRAIL and ALDH1+ tumor cell are used as treatment and prognosis makers for the patients with NSCLC. This study has important significance to clarify the mechanism of sTRAIL in inhibiting cancer stem cells.

英文关键词： cancer stem cell;ALDH1;sTRAIL;NSCLC;apoptosis