清晰细胞肾癌（ccRCC）有着不良的临床结局，需要新的治疗选择。表皮生长因子受体（EGFR）是一个潜在的治疗靶点，因为它与各种癌症的进展有关。牛蒡中的一种天然化合物——牛蒡苷，已被证明在各种癌症中具有抗癌能力。使用牛蒡苷和抗-ccRCC药物进行了细胞测定和联合研究。使用ccRCC异种移植小鼠模型确定了牛蒡苷的体内有效性。应用免疫印迹和生物化学分析来研究受牛蒡苷影响的信号。牛蒡苷抑制ccRCC细胞的生长、迁移和存活，同时保留正常的肾细胞。牛蒡苷与5-FU和索拉非尼协同作用，但与替莫唑酮没有协同作用，可以抑制ccRCC细胞的生长。在ccRCC异种移植小鼠模型中进一步显示了牛蒡苷与5-FU和索拉非尼的协同作用。牛蒡苷与临床抗RCC药物的联合使用完全抑制了肿瘤的生长，甚至在长时间的治疗期间都没有出现肿瘤进展。机理上，牛蒡苷的抑制方式是通过抑制EGFR介导的信号通路来抑制生长，而依赖于RhoA的方式来抑制迁移。我们的研究结果表明，将牛蒡苷添加到当前的ccRCC治疗中效果良好，并证实了EGFR作为治疗RCC的靶点的价值。

Clear cell renal cell carcinoma (ccRCC) has poor clinical outcomes and necessitates new treatment options. Epidermal growth factor receptor (EGFR) is a potential therapeutic target, due to the associations with various carcinomas' progression. Arctigenin, a natural compound of Arctium lappa, has been shown to display anticancer abilities in various carcinomas. Cellular assays and combination studies were conducted using arctigenin and anti-ccRCC drugs. In vivo efficacy of arctigenin was determined using ccRCC xenograft mouse model. Immunoblotting and biochemistry analysis were applied to investigate the signaling affected by arctigenin. Arctigenin inhibits growth, migration, and survival of ccRCC cells while sparing normal kidney cells. Arctigenin acts synergistically with 5-FU and sorafenib but not temsirolimus in inhibiting ccRCC cells. Synergism of arctigenin with 5-FU and sorafenib was further shown in ccRCC xenograft mouse model. The combination of arctigenin with clinical anti-RCC drugs completely inhibits tumor growth without tumor progression even for an extended time period. Mechanistically, arctigenin inhibits migration in a RhoA-dependent manner while inhibits growth via suppressing EGFR-mediated signaling pathways. Our findings suggest that arctigenin performs well to add to current treatment in ccRCC and confirm the value to target EGFR to improve therapy in RCC.