铂类药物治疗被广泛应用于治疗转移性结直肠癌。然而，长期重复使用药物治疗导致耐药和化疗失败。早先就有报道称各种天然化合物能够作为化疗增敏剂，逆转药物耐药。在本研究中，我们发现广花桔梗中的皂苷素D（PD）抑制了LoVo和OR-LoVo细胞的增殖、侵袭和迁移能力。我们的研究结果表明，联合使用铂类药物和PD可以显著降低LoVo和OR-LoVo细胞的细胞增殖。此外，PD的治疗剂量依赖性降低了LATS2/YAP1的海马信号和生存标志物p-AKT的表达，并增加了细胞周期蛋白相关激酶抑制物蛋白如p21和p27的表达。重要的是，PD通过泛素化和蛋白酶体途径激活并促进YAP1的降解。 PD治疗下YAP的核转录活性显著降低，导致下游基因调节细胞增殖，促进生存和转移的转录抑制。综上所述，我们的研究结果表明，PD作为一种有前途的药物可以克服铂类药物耐药的结直肠癌。© 作者（们）。

Oxaliplatin-based therapy is used as a first-line drug to treat metastatic colorectal cancer. However, long-term and repeated drug treatment resulted in drug resistance and the failure of chemotherapy. Various natural compounds were previously reported to act as chemosensitizers to reverse drug resistance. In this study, we found that platycodin D (PD), a saponin found in Platycodon grandiflorum, inhibited LoVo and OR-LoVo cells proliferation, invasion, and migration ability. Our results indicated that combined treatment of oxaliplatin with PD dramatically reduced the cellular proliferation in both LoVo and OR-LoVo cells. Furthermore, treatment with PD dose-dependently decreased LATS2/YAP1 hippo signaling and survival marker p-AKT expression, as well as increased cyclin-dependent kinase inhibitor proteins such as p21 and p27 expression. Importantly, PD activates and promotes YAP1 degradation through the ubiquitination and proteasome pathway. The nuclear transactivation of YAP was significantly reduced under PD treatment, leading to transcriptional inhibition of the downstream genes regulating cell proliferation, pro-survival, and metastasis. In conclusion, our results showed that PD is suitable as a promising agent for overcoming oxaliplatin-resistant colorectal cancer.© The author(s).