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Modulatory effect of euxanthone in liver cancer-bearing obese mice: crosstalk between PPARγ and TIMP3 signalling axes

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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.

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Authors and Affiliations

  1. Department of General Surgery, Weinan Central Hospital, Weinan, 714000, Shaanxi, China

    Xu Wang, Zhanhong Wang, Qian Wang & Baoquan Wang

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  1. Xu Wang
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  2. Zhanhong Wang
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  3. Qian Wang
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  4. Baoquan Wang
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Contributions

Conceptualization XW, ZW, QW, and BW; methodology XW, ZW, QW, and BW; formal analysis and investigation XW and ZW; writing—original draft preparation XW and BW; writing—review and editing critically for important intellectual content BW; supervision BW.

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Correspondence to Baoquan Wang.

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All the authors declare that there is no conflict of interest.

Ethical approval

The informed consent was sought from the patients before inclusion in the present study and the study was approved by the research ethics committee of Weinan Central Hospital, Weinan, Shaanxi, China with approval number WCH-002/20.

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Wang, X., Wang, Z., Wang, Q. et al. Modulatory effect of euxanthone in liver cancer-bearing obese mice: crosstalk between PPARγ and TIMP3 signalling axes. 3 Biotech 11, 464 (2021). https://doi.org/10.1007/s13205-021-03019-9

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  • DOI: https://doi.org/10.1007/s13205-021-03019-9

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