败酱草总皂苷通过LncRNA NKILA/NF-κB/NLRP3信号通路调控细胞焦亡发挥抗结肠癌侵袭转移的机制研究

侵袭转移是造成结直肠癌不良预后的主要因素，细胞焦亡能够抑制结直肠癌侵袭转移。因此，寻找诱导细胞焦亡的策略是结直肠癌治疗的重点。申请人前期研究中证实败酱草总皂苷可以上调LncRNA NKILA诱导结直肠癌细胞焦亡，抑制结直肠癌侵袭转移，其机制可能与NKILA参与下NLRP3信号相关。由此，我们推测：败酱草总皂苷通过NKILA下调NF-κB而抑制NLRP3，从而诱导细胞焦亡发生，抑制结直肠癌侵袭转移。为验证该假说，本项目将从临床、细胞、动物三个层面，采用基因编辑、小动物活体成像等技术，来明确NKILA通过调控NF-κB/NLRP3信号通路，促进结直肠癌细胞焦亡机制，阐明败酱草总皂苷通过LncRNA NKILA/NF-κB/NLRP3信号轴介导细胞焦亡抑制结直肠癌侵袭转移的作用机理，为中医药防治结直肠癌提供理论指导和实验依据。

Invasion and metastasis is the main factor leading to poor prognosis of colorectal cancer. Pyroptosis can inhibit the invasion and metastasis of colorectal cancer. Therefore, finding strategies to induce pyroptosis is the focus of the treatment of colorectal cancer. The previous study of the applicant confirmed that total saponins of Patrinia scabra can activate the pyroptosis of colorectal cancer cells via up-regulation of LncRNA NKILA to inhibit the invasion and metastasis. The mechanism may be related to the NLRP3 signal under the participation of NKILA. Therefore, we speculate that total saponins of Patrinia frutescens can down-regulate NF-κB and inhibit NLRP3, through NKILA, which can induce cell pyroptosis and inhibit the invasion and metastasis of colorectal cancer. In order to verify this hypothesis, this project will use gene editing and in vivo imaging techniques from the clinical, cellular and animal levels to clarify the mechanism of NKILA promoting the pyroptosis of colorectal cancer cells by regulating NF- κ B/NLRP3 signal pathway, and elucidate the mechanism of total saponins of Patrinia frutescens in inhibiting the invasion and metastasis of colorectal cancer through LncRNA NKILA/NF-κB/NLRP3 signal axis. To provide theoretical guidance and experimental basis for the prevention and treatment of colorectal cancer with traditional Chinese medicine.