PPARα Enhances Cancer Cell Chemotherapy Sensitivity by Autophagy Induction.
Mengli YouJiaming GaoJianhua JinYongzhong HouPublished in: Journal of oncology (2018)
PPARα (peroxisome-proliferator-activated receptor α) plays a critical role in regulation of inflammation and cancer, while the regulatory mechanism of PPARα on cancer cell autophagy is still unclear. Here we found that PPARα enhanced autophagy in HEK293T, SW480, and Hela cell lines, which was independent of PPARα transcription activity. PPARα induced antiapoptotic Bcl2 protein degradation resulting in release of the Beclin-1/VPS34 complex. Consistently, silenced PPARα reversed this event. PPARα-induced autophagy significantly inhibited tumor growth and enhanced SW480 cancer cell sensitivity to chemotherapy drugs. Moreover, PPARα agonist increased SW480 cancer cell chemotherapy sensitivity. These findings revealed a novel mechanism of PPARα/Bcl2/autophagy pathway suppressed tumor progression and enhanced chemotherapy sensitivity, which is a potential drug target for cancer treatment.
Keyphrases
- insulin resistance
- cell death
- oxidative stress
- endoplasmic reticulum stress
- signaling pathway
- fatty acid
- emergency department
- diabetic rats
- metabolic syndrome
- adipose tissue
- type diabetes
- high glucose
- radiation therapy
- young adults
- risk assessment
- cell proliferation
- endothelial cells
- lymph node metastasis
- human health
- pi k akt
- adverse drug