Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway
Chien-Hao Wang, Rathinasamy Baskaran, Shawn Shang-Chuan Ng, Tso‐Fu Wang, Chi‐Cheng Li, Tsung‐Jung Ho, Dennis Jine‐Yuan Hsieh, Chia‐Hua Kuo, Ming‐Cheng Chen, Chih‐Yang Huang
Abstract
, 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.