Pioglitazone inhibits EGFR/MDM2 signaling-mediated PPARγ degradation

作者：Shi, Juanjuan; Zhang, Wenbo; You, Mengli; Xu, Ying; Hou, Yongzhong; Jin, Jianhua^*

来源：European Journal of Pharmacology, 2016, 791: 316-321.

DOI：10.1016/j.ejphar.2016.09.010

• Pioglitazone
• PPAR gamma
• EGFR
• Ubiquitination
• Degradation

Aberrant activation of the epidermal growth factor receptor (EGFR) signaling is involved in many cancer events. Although peroxisome proliferator-activated receptor gamma (PPAR gamma) has been implicated in inhibition of inflammation and cancer, EGFR/MDM2 signaling induces PPAR gamma phosphorylation and degradation. Here we found that cancer cells in response to EGF reduced PPAR gamma protein levels by inducing its phosphorylation, ubiquitination and degradation, but PPAR gamma agonist pioglitazone reversed this event. More importantly, pioglitazone increased cancer cell sensitivity to chemotherapy drugs. Therefore, our study revealed a novel mechanism that pioglitazone inhibited EGFR/MDM2-mediated cancer cell chemoresistance, which provides a novel strategy for cancer treatment.

• 出版日期2016-11-15
• 单位江苏大学