Platycodin D Enhances Glioma Sensitivity to Temozolomide by Inhibition of the Wnt/β-Catenin Pathway

Haima Li,1,* Jia Ouyang,2,* Xuelian Wang,3 Chao Qian1 1Department of Neurosurgery, The Nuclear Industry 215 hospital of Shaanxi Province, Xianyang, Shaanxi, 712000, People’s Republic of China; 2Department of Neurosurgery, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 3Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia Ouyang, Email [email protected] Chao Qian, Email [email protected]: Temozolomide (TMZ) is a first-line chemotherapeutic agent for gliomas. However, its efficacy is limited by drug resistance. Platycodin D (PD) exhibits notable anti-glioma activity The objective of this study was to investigate the potential of PD to augment glioma sensitivity to TMZ and the underlying mechanisms.Methods: Cell viability and proliferation were assessed using CCK-8 and clonogenic assays, respectively, while flow cytometry was used to detect apoptosis. Cell migration and invasion were assessed using Transwell assays. Western blotting and immunohistochemistry analyses were performed to determine protein expression levels. A xenograft glioma model was established to investigate the in vivo effects of PD.Results: PD augmented glioma cell sensitivity to TMZ, as evidenced by heightened inhibition of cell growth, colony formation, migration, and invasion, accompanied by elevated apoptosis. Treatment with PD or a combination of PD and TMZ robustly suppressed the expression of active β-catenin and c-Myc, which was reversed by the β-catenin activator, SKL2001. In vivo experiments demonstrated that PD amplified the anti-glioma efficacy of TMZ, resulting in diminished Ki67 expression and substantially reduced expression of active β-catenin and c-Myc in the tumor tissue.Conclusion: PD augmented glioma cell sensitivity to TMZ by modulating Wnt/β-catenin pathway. Our findings demonstrate the potential of PD as an innovative therapeutic agent to enhance glioma treatment, especially in TMZ-resistant gliomas.Keywords: platycodin D, TMZ, Wnt/β-catenin pathway, glioma