重楼皂苷诱导循环肿瘤细胞失巢凋亡抑制肺癌转移的作用及机制研究

循环肿瘤细胞（CTCs）在转移中起关键作用，但肺癌转移防治策略缺乏对CTCs的精准干预。课题组前期研究发现早期肺癌患者高表达CTCs，并成功建立人肺癌CTCs细胞系。单细胞测序证实该CTCs来自原发灶，且具有耐药性强和肺转移能力。研究发现以重楼皂苷为主要成份的金复康口服液可诱导CTCs失巢凋亡，抑制TrkB的表达。而BDNF/TrkB介导的CTCs失巢凋亡抵抗是转移发生的关键。据此提出“重楼皂苷调控BDNF/TrkB通路诱导CTCs失巢凋亡防治肺癌转移”的假说。拟采用尾静脉注射CTCs建立肺转移模型，动态监测外周血中CTCs数目和肺转移灶；评估重楼皂苷抑制转移发生的作用；并模拟CTCs所处体内生存状态，建立悬浮培养体系评估重楼皂苷诱导CTCs失巢凋亡的作用机制。期望从CTCs失巢凋亡的角度揭示重楼皂苷“清伏毒”防转移的本质，从而丰富肺癌的病因病机认识。创建基于CTCs的肺转移研究技术模型。

Circulating tumor cells (CTCs) play a key role in metastasis, but the prevention and control strategy of lung cancer metastasis is lack of precise intervention for CTCs. Our previous study found that lung cancer patients have a large number of CTCs in the early stage, and successfully established human lung cancer CTCs cell line. Single-cell sequencing found that the CTCs came from the primary tumor, and has strong drug resistance and lung metastases. Our study found that Jinfukang oral liquid, the main component of which is polyphyllin, can induce anoikis of CTCs and inhibit the expression of TrkB protein. And anoikic resistance of CTCs mediated by BDNF/TrkB pathway is the key to metastasis. Based on this, we put forward the hypothesis of “polyphyllin promote the anoikis of CTCs to prevent the metastasis of lung cancer through regulating the BDNF/TrkB pathway”. In our study, we establish the lung metastasis model by intravenous injection of CTCs, dynamically monitor the number of CTCs in the peripheral blood and lung metastases, to evaluate the role of polyphyllin in inhibiting metastasis. And that we simulate the internal environment of CTCs, establish suspension culture system to study the mechanism of the anoikis of CTCs induced by polyphyllin. The study expects to reveal the nature of polyphyllin prevent metastasis by “clear poison” from the perspective of anoikis resistance of CTCs, thereby enriching the etiology and pathogenesis of lung cancer. Meanwhile, we are also looking forward to establish a technology model for lung metastasis research based on CTCs.