中文摘要
肿瘤干细胞理论认为肿瘤干细胞是引起肿瘤复发转移的根本原因,非编码RNA对肿瘤干细胞干性维持和诱导肿瘤细胞分化发挥着重要的作用。已有研究证实ROR可作为竞争性内源RNA可以影响细胞凋亡、信号通路和肿瘤转移侵袭等诸方面。本课题组前期研究发现清胰化积方明显抑制胰腺癌干细胞分化,而且能下调长链非编码RNA ROR和肿瘤干细胞核转录因子OCT4表达;同时,内在机制研究发现lncRNA-ROR对OCT4具有特异性调控作用,但lncRNA-ROR通过何种途径调控OCT4进而影响肿瘤干细胞则需要进一步深入研究。因此,本研究以lncRNA-ROR对胰腺癌肿瘤干细胞转录因子OCT4调控作用为切入点,明确其对胰腺癌干细胞自我更新、分化、侵袭、转移及耐药等影响,探索胰腺癌患者清胰化积方治疗后长期带瘤生存的内在机制,将对诠释中医药抗肿瘤治疗中带瘤生存现象提供新思路和新方法。
英文摘要
The cancer stem cells (CSCs) hypothesis assumed that CSCs are essential for cancer metastasis. Recent studies have indicated that long non-coding RNA (lncRNA) is involved in the multiple biological processes, including carcinogenesis. ROR is a competitive endogenous RNA that plays an important regulatory role in the pathogenesis and progression of cancer. While the lncRNAs that participate in cancer progression remain unknown. Our previous studies found QYHJ formula inhibit pancreatic cancer stem cells (PCSCs), but also reduced long non-coding RNA ROR and tumor stem cell nuclear transcription factors OCT4; at the same time, we found that ROR is specific for OCT4, but how ROR regulates OCT4 then affecting the cancer stem cells will need further study. In this project, it is designed to construct PCSC/ROR RNAi cells to explore the role of ROR in pancreatic cancer stem cells. Then to verify the outcomes in vitro experiment, subcutaneous xenograft model and liver metastasis model will be established to investigate the different regulative effect of QYHJ on potency of pancreatic cancer stem cells with different expression status of ROR. The project will investigate the mechanism of patients' survival with tumor by QYHJ formula treatment and also provide with new idea and the therapeutic target for pancreatic cancer by traditional Chinese medicines.
