Feng Jiang1, Minghao Liu2, Haidan Wang3, Guoping Shi3, Biqing Chen3, Tuo Chen4, Xiaomin Yuan4, Ping Zhu1, Jinyong Zhou3, Qiong Wang5, Yugen Chen6. 1. Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China. 2. Department of Colorectal Surgery, Siyang Hospital of Tradition Chinese Medicine, Suqian 223700, China. 3. Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China. 4. No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China. 5. Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China. Electronic address: calcspar@163.com. 6. Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China. Electronic address: Chenyg666@126.com.
Abstract
BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality rate worldwide. Colitis-associated CRC (CAC) is used for describing the relationship between inflammation and CRC. No chemopreventive agents have been found to be both effective and safe in CRC. Therefore, the prevention and treatment of CAC are extremely urgent. Wu Mei Wan (WMW) has been used for the clinical treatment of enteritis with a remarkable efficacy. Here, we aim to investigate the underlying mechanism of WMW in the prevention of CAC. METHODS: The AOM/DSS-induced CAC mouse model was used, and the mice were divided into normal control (NC), AOM/DSS model control (MC), and AOM/DSS plus WMW (WMW). The weight of mice, the score of DAI, survival rate, number of tumors and sample collection were performed at the end of the 14th week. Histopathological examination was performed using Hematoxylin-Eosin (HE) staining. Tumor cell proliferation was indicated by the expression of PCNA, and p65 and p-STAT3 were detected by immunohistochemistry. Serum IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). The expression of p65, IL-6 and p-STAT3 in the colon was detected by Western Blot. Intestinal flora was analyzed by 16S rDNA sequencing. RESULTS: WMW improved the survival rate of mice in the MC group and also attenuated CAC symptoms such as abnormal clinical colitis and pathological changes to intestinal tissue by reducing DAI score, tumor formation, tumor volume, and grade of tumorigenesis. WMW also reduced the proliferation of tumor cells in colon tissues. WMW decreased the expression of p65, IL-6, and p-STAT3 in colon tumors of CAC mice. WMW decreased Bacteroidetes and increased Firmicutes at the phylum level, while decreasing bacteroidales_s24-7_group and increasing the number of Lachnospiraceae at the family level. CONCLUSION: WMW attenuates CAC by regulating the balance between "tumor-promoting bacteria" and "tumor-suppressing bacteria" and the NF-kB/IL-6/STAT3 pathway. WMW has the potential to be a safe and effective chemopreventive drug but further clinical evidence is necessary.
BACKGROUND:Colorectal cancer (CRC) has a high incidence and mortality rate worldwide. Colitis-associated CRC (CAC) is used for describing the relationship between inflammation and CRC. No chemopreventive agents have been found to be both effective and safe in CRC. Therefore, the prevention and treatment of CAC are extremely urgent. Wu Mei Wan (WMW) has been used for the clinical treatment of enteritis with a remarkable efficacy. Here, we aim to investigate the underlying mechanism of WMW in the prevention of CAC. METHODS: The AOM/DSS-induced CAC mouse model was used, and the mice were divided into normal control (NC), AOM/DSS model control (MC), and AOM/DSS plus WMW (WMW). The weight of mice, the score of DAI, survival rate, number of tumors and sample collection were performed at the end of the 14th week. Histopathological examination was performed using Hematoxylin-Eosin (HE) staining. Tumor cell proliferation was indicated by the expression of PCNA, and p65 and p-STAT3 were detected by immunohistochemistry. Serum IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). The expression of p65, IL-6 and p-STAT3 in the colon was detected by Western Blot. Intestinal flora was analyzed by 16S rDNA sequencing. RESULTS: WMW improved the survival rate of mice in the MC group and also attenuated CAC symptoms such as abnormal clinical colitis and pathological changes to intestinal tissue by reducing DAI score, tumor formation, tumor volume, and grade of tumorigenesis. WMW also reduced the proliferation of tumor cells in colon tissues. WMW decreased the expression of p65, IL-6, and p-STAT3 in colon tumors of CAC mice. WMW decreased Bacteroidetes and increased Firmicutes at the phylum level, while decreasing bacteroidales_s24-7_group and increasing the number of Lachnospiraceae at the family level. CONCLUSION: WMW attenuates CAC by regulating the balance between "tumor-promoting bacteria" and "tumor-suppressing bacteria" and the NF-kB/IL-6/STAT3 pathway. WMW has the potential to be a safe and effective chemopreventive drug but further clinical evidence is necessary.