紫杉醇是近些年发现的抑癌效果较好的化疗药，但极易产生耐药性。我们前期工作发现，在肝癌Hep3B细胞中Lin28B过高表达，它通过阻碍let-7的成熟增加下游抗凋亡基因Bcl-xL的表达，导致细胞凋亡逃逸，从而提高了肝癌细胞对紫杉醇的耐药性。进一步研究表明姜黄素能够抑制Hep3B细胞Lin28B的表达并增加细胞对紫杉醇的敏感度，我们推测可能与其下调Lin28B的转录激活因子NF-κB的活性有关。本研究拟通过筛选肝癌细胞紫杉醇耐药株并建立裸鼠肝癌转移瘤耐药模型，进一步明确姜黄素逆转紫杉醇耐药的特性；采用RNA干扰、过表达等技术验证Lin28B/let-7/Bcl-xL通路与肝癌细胞紫杉醇耐药的相关性；采用流式、ChIP、EMSA等技术研究姜黄素通过NF-κB调控Lin28B/let-7/Bcl-xL通路逆转紫杉醇耐药的分子机制，为联合用药治疗肝癌探索一条新的思路。

Paclitaxel, an efficient anti-cancer chemotherapy drug, is easy to produce drug-resistance. Our previous work found that paclitaxel-resistance enhanced as well as Lin28B expression increased, allowing Hep3B cells to escape from apoptosis and acquire a survival advantage caused by inhibiting maturation of let-7, which will increase the expression of anti-apoptosis gene Bcl-xL. We also found that.curcumin increased the sensitive of HCC cells to paclitaxel, probably through inhibiting the activity of NF-κB which is the transcription activator of Lin28B. In order to confirm our hypothesis, we will establish paclitaxel resistant human hepatocellular carcinoma cell strains and mouse metastatic human hepatocellular carcinoma models to thoroughly enunciate the effect of curcumin on reversing paclitaxel-resistance. Experiment techniques such as RNA interference, over-expression are taken to verify the relationship between Lin28B/let-7/Bcl-xL pathway and paclitaxel resistance in HCC cells. Flow cytometry, ChIP, EMSA are taken to investigate the underlying mechanism of curcumin on reversing paclitaxel-resistance via Lin28B/let-7/Bcl-xL pathway regulated by NF-κB. This research will provide a new strategy for drug combination studies on HCC.