Abstract 1859: Quxie capsule inhibits the colon tumor growth through modulating the gut microbiome and tumor myosin 11 expression

Abstract

Abstract Traditional Chinese Herbal Medicine formula, such as the Quxie Capsule (QXC), has been used for advanced colorectal cancer treatment with favorable clinical outcome at Xiyuan Hospital in Beijing, China. However, the mechanism(s) underlying the anticancer effect of QXC in colon cancer still remain unclear, which hampers its optimal use for the treatment of colon cancer. The purpose of this study is to examine whether, and if yes, how QXC exerts anti-tumor activity via alteration of gut microbiota and related pathways. The antitumor efficacy of QXC was tested in CT-26 syngeneic mouse colon cancer models. Gut microbiome was measured by 16sRNA sequencing in fecal samples. Signaling protein expression profile in tumor tissues was assessed by RPPA and validated by Western blot. QXC gavaged to mice carrying CT26 tumors for 2 weeks significantly reduced the average tumor weight (0.92 ± 0.15g) compared to that of the vehicle control (1.57 ± 0.1689, p < 0.05). In contrast, when mice bearing CT26 tumor were pretreated antibiotics, the tumor weight (0.51±0.11g) in QXC treated mice was not statistically significantly smaller than that of vehicle control (0.76±0.13g, p>0.05). Mice pretreated with vehicle for 12 days then transplanted with fecal from QXC treated mice had smaller tumor compared with vehicle only group (p<0.05). Similarly, the tumor in mice pretreated with QXC and followed by transplantation of fecal from vehicle control mice grew faster than that of QXC treated alone, but not statistically significant (p>0.05). The result of 16sRNA sequencing showed that the ratio of Firmicutes over Bacteriodetes (F/B) was decreased by 2.03 folds in tumor-bearing mice compared to non-tumor-bearing mice (p<0.05). Intriguingly, QXC led to an increase of Firmicutes and reduction of Bacteriodetes and resulted in a 2.0-fold increase in the ratio of F/B compared to that prior to QXC treatment (p<0.05). The OTUs were significantly and markedly decreased (p<0.05) after antibiotics treatment. Both alpha and beta diversity in antibiotic and QXC co-treated mice were similar to that of the vehicle control and antibiotic co-treated group. The result of RPPA showed that protein Myosin 11, which was downregulated in fiber-deprived colon mucosa, was significantly elevated in QXC treated tumor tissues compared to that of control (p<0.05). In contrast, Myosin 11 expression was lower in the tumor tissues of antibiotics and QXC co-treated mice compared to that of antibiotics and vehicle control co-treatment group. QXC elicited upregulation of Myosin 11 protein expression was further validated in QXC treated CT-26 cells in vitro. In conclusion, QXC inhibited the growth of colon tumors, which could be due to its ability to rebalance the intestinal microbiota and upregulate the myosin 11 level in the syngeneic colon cancer model. Note: This study was partially founded by National Natural Science Foundation of China (No. 81373824). Citation Format: Dongmei Chen, Daoyuan Wei, Yufei Yang, Peiying Yang. Quxie capsule inhibits the colon tumor growth through modulating the gut microbiome and tumor myosin 11 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1859.