健脾解毒方通过NF-κB调节Nrf2/MRP2信号通路逆转大肠癌多药耐药的作用机制

多药耐药是导致大肠癌化疗失败的主要原因之一，MRP2蛋白在多药耐药中发挥重要作用。课题组前期发现，Nrf2能够调控MRP2介导的大肠癌多药耐药，健脾解毒方能够逆转大肠癌多药耐药，并能下调NF-κB、Nrf2及MRP2的表达，但Nrf2/MRP2是通过什么途径调控的尚不清楚。最新研究表明NF-κB能够启动Nrf2转录，而Nrf2表达上调及核转位是引起MRP2基因转录的重要因素之一。因此，我们提出假说NF-κB可能是调控Nrf2/MRP2信号通路介导的大肠癌耐药的重要途径之一；健脾解毒方可能通过NF-κB调节Nrf2/MRP2信号通路逆转大肠癌耐药。. 本研究通过荧光免疫染色、流式细胞术、小动物活体成像等方法，探讨健脾解毒方对NF-κB/Nrf2/MRP2信号传递介导的大肠癌耐药的调控机制。这对于揭示大肠癌耐药的机理，明确中药防治大肠癌耐药的新途径，具有重要的临床意义。

Resistance to chemotherapy limits the effectiveness of colorectal cancer. MRP2 transporters play an important role in multidrug resistant colorectal cancer. We previously showed that the activation of Nrf2/MRP2 signaling pathway can mediate the occurrence of multidrug resistance in colorectal cancer. Meanwhile, Jianpi Jiedu Recipe could reverse drug resistance of human colorectal cancer, down regulate the expressions of NF-κB and MRP2, and prevent nuclear translocation of Nrf2. However, the regulatory mechanism of Nrf2/MRP2 signaling pathway is unclear. Recent study showed that NF-κB could activate the transcription of Nrf2 gene, and the increase of protein expression and nuclear translocation of Nrf2 are one of the important factors of MRP2 gene transcription. Therefore, we hypothesized that NF-κB may be the reason of Nrf2/MRP2 signaling pathway mediated drug resistance in colorectal cancer and Jianpi Jiedu Recipe may reverse drug resistance via NF-κB/Nrf2/MRP2 signaling pathway in colorectal cancer. .In this study, we explore the effect of Jianpi Jiedu Recipe in NF-κB/Nrf2/MRP2 signaling mediated drug resistance in colorectal cancer cells through immunofluorescence staining, flow cytometry and other experimental technologies. It will be helpful to elucidate molecular mechanism and find the new way in the prevention and treatment of drug-resistant colorectal cancer.