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PPAR? Enhances Cancer Cell Chemotherapy Sensitivity by Autophagy Induction.


ABSTRACT: PPAR? (peroxisome-proliferator-activated receptor ?) plays a critical role in regulation of inflammation and cancer, while the regulatory mechanism of PPAR? on cancer cell autophagy is still unclear. Here we found that PPAR? enhanced autophagy in HEK293T, SW480, and Hela cell lines, which was independent of PPAR? transcription activity. PPAR? induced antiapoptotic Bcl2 protein degradation resulting in release of the Beclin-1/VPS34 complex. Consistently, silenced PPAR? reversed this event. PPAR?-induced autophagy significantly inhibited tumor growth and enhanced SW480 cancer cell sensitivity to chemotherapy drugs. Moreover, PPAR? agonist increased SW480 cancer cell chemotherapy sensitivity. These findings revealed a novel mechanism of PPAR?/Bcl2/autophagy pathway suppressed tumor progression and enhanced chemotherapy sensitivity, which is a potential drug target for cancer treatment.

SUBMITTER: You M 

PROVIDER: S-EPMC6241347 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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PPAR<i>α</i> Enhances Cancer Cell Chemotherapy Sensitivity by Autophagy Induction.

You Mengli M   Gao Jiaming J   Jin Jianhua J   Hou Yongzhong Y  

Journal of oncology 20181104


PPAR<i>α</i> (peroxisome-proliferator-activated receptor <i>α</i>) plays a critical role in regulation of inflammation and cancer, while the regulatory mechanism of PPAR<i>α</i> on cancer cell autophagy is still unclear. Here we found that PPAR<i>α</i> enhanced autophagy in HEK293T, SW480, and Hela cell lines, which was independent of PPAR<i>α</i> transcription activity. PPAR<i>α</i> induced antiapoptotic Bcl2 protein degradation resulting in release of the Beclin-1/VPS34 complex. Consistently,  ...[more]

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