OncoTargets and Therapy (Aug 2020)
Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice
Abstract
Yi-feng Zou,1,2,* Yu-ming Rong,3,* Ze-xian Chen,1,2,* Zhi-hong Shen,4 Xi Chen,1,2 Ying-xin Tan,1,2 Jing-rong Weng,1,2 Xiao-ming Huang,2,5 Xu-tao Lin2,6 1Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Very Important Person Region, Cancer Center of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Department of General Surgery, Jieyang Hospital of Traditional Chinese Medicine, Jieyang, Guangdong, People’s Republic of China; 5Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Gastrointestinal Endoscopy, Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu-tao Lin; Xiao-ming Huang Email [email protected]; [email protected]: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC.Methods: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry.Results: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1β) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice.Conclusion: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.Keywords: colorectal cancer, Huaier extract, colitis, traditional Chinese medicine
