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- Title
Modulatory effect of euxanthone in liver cancer-bearing obese mice: crosstalk between PPARγ and TIMP3 signalling axes.
- Authors
Wang, Xu; Wang, Zhanhong; Wang, Qian; Wang, Baoquan
- Abstract
Liver cancer is one of the prominent cancer-associated fatal diseases with > 80% of cases befall in low–middle resource nations worldwide. In the current study, we studied the effect of euxanthone (EUX) on obesity-associated liver cancer using a high-fat diet-fed mouse model of diethylnitrosamine (DEN)-provoked hepatocellular carcinoma. Mice with 2 weeks of age were intraperitoneally injected with diethylnitrosamine (DEN) 25 mg/kg b.w. After 4 weeks, the mice were divided into four groups with low-fat diet (LFD), high-fat diet (HFD), and EUX treatment groups with or without PPARγ inhibitor (GW9662). We observed that TIMP3, E-cadherin, and Klotho expressions were downmodulated, while MMP9, ADAM17, and Wnt signalling biofactors (Wnt5a, Wnt3a and β-catenin) were upmodulated in the HFD groups. Nevertheless, these aberrations were reciprocated by the treatment with EUX; at the same time, co-administration of PPARγ inhibitor ablated the anti-cancer effects of EUX, indicating that PPARγ activation is a pivotal mechanism underpinning the negative regulation of oncogenic factors by EUX. Together, these results imply that EUX might be a viable therapeutic option in the treatment of obesity-associated hepatocarcinogenesis.
- Subjects
LIVER cancer; LABORATORY mice; LOW-fat diet; HIGH-fat diet; HEPATOCELLULAR carcinoma; LIVER
- Publication
3 Biotech, 2021, Vol 11, Issue 11, p1
- ISSN
2190-572X
- Publication type
Article
- DOI
10.1007/s13205-021-03019-9