1. Ursolic acid-enriched kudingcha extract enhances the antitumor activity of bacteria-mediated cancer immunotherapy.
- Author
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Xu, Haixia, Piao, Linghua, Liu, Xiande, and Jiang, Sheng-nan
- Subjects
COLON tumors ,DRUG efficacy ,HOST-bacteria relationships ,HIGH performance liquid chromatography ,STAINS & staining (Microscopy) ,ANIMAL experimentation ,WESTERN immunoblotting ,LOG-rank test ,CELL receptors ,PHYTOCHEMICALS ,PATHOLOGIC neovascularization ,LEAVES ,SALMONELLA ,DESCRIPTIVE statistics ,KAPLAN-Meier estimator ,SURVIVAL analysis (Biometry) ,RESEARCH funding ,PLANT extracts ,COMBINED modality therapy ,URSOLIC acid ,VASCULAR endothelial growth factors ,IMMUNOTHERAPY ,BACTERIA ,MICE ,LUMINESCENCE spectroscopy ,PHOSPHORYLATION - Abstract
Background: Bacteria-mediated cancer immunotherapy (BCI) robustly stimulates the immune system and represses angiogenesis, but tumor recurrence and metastasis commonly occur after BCI. The natural product Ilex kudingcha C. J Tseng enriched with ursolic acid has anti-cancer activity and could potentially augment the therapeutic effects of BCI. The objective of the present study was to determine potential additive effects of these modalities. Methods: We investigated the anti-cancer activity of KDCE (Kudingcha extract) combined with S.t△ppGpp in the mice colon cancer models. Results: In the present study, KDCE combined with S.t△ppGpp BCI improved antitumor therapeutic efficacy compared to S.t△ppGpp or KDCE alone. KDCE did not prolong bacterial tumor-colonizing time, but enhanced the antiangiogenic effect of S.t△ppGpp by downregulatingVEGFR2. We speculated that KDCE-induced VEGFR2 downregulation is associated with FAK/MMP9/STAT3 axis but not AKT or ERK. Conclusions: Ursolic acid-enriched KDCE enhances the antitumor activity of BCI, which could be mediated by VEGFR2 downregulation and subsequent suppression of angiogenesis. Therefore, combination therapy with S.t△ppGpp and KDCE is a potential cancer therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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