Abstract

Colitis-associated cancer (CAC) is a malignant disease of the colon that is caused by recurrent episodes of chronic intestinal inflammation. Huangqi Baizhu decoction (HBD) is a classic prescription comprised of Radix Astragali and Rhizoma Atractylodis, which are usually used to treat digestive conditions, such as peptic ulcers, colitis, or colorectal carcinoma in clinics. HBD is well known for “tonifying qi and spleen” based on the theories of traditional Chinese medicine, and has the preponderant effect of alleviating chronic intestinal mucosa damage associated with disease. However, the underlying mechanism behind this is still unknown. In the current study, we employed the AOM/DSS mouse model to analyze the effects of HBD on the development of inflammation in colonic carcinoma. The in vivo study showed that HBD could significantly reduce the mortality of mice and control the incidence and size of colonic tumors by inhibiting the IL-6/STAT3 signaling pathway. In vitro, Astragaloside and Atractylenolide (CAA), the main components of HBD, inhibited the proliferation of HCT-116 cells as determined by an MTT assay. Furthermore, CAA notably suppressed the protein expression of IL-6R, STAT3, Survivin, and Cyclin D1 induced by IL-6 in HCT-116 and RAW264.7 cells. These results suggested that HBD exhibits anti-inflammatory and anti-proliferative effects, inhibiting the development of CAC in mice.

Highlights

  • Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease with unknown etiology

  • The treatment of colorectal cancer is mainly based on surgical treatments, such as laparoscopic surgery for primary tumors, and surgical resection is employed for treating metastatic tumors affecting organs, such as the liver and lungs

  • We used an AOM/DSS murine model to investigate the effects of Huangqi Baizhu decoction (HBD) on colitis-associated cancer, and the underlying mechanisms were explored

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Summary

Introduction

Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease with unknown etiology. Colorectal carcinoma is the most severe prognosis for UC, and the incidence of colitis-associated cancer (CAC) is 4 to 10 times higher than sporadic colorectal cancer It ranks as the third most common malignant tumor in developed countries, such as European nations and the United States. Chronic intestinal inflammation facilitates pro-inflammatory cytokine production and cell proliferation, and affects immune responses, promoting tumorigenesis in CAC [6,7]. Huangqi Baizhu decoction (HBD) is a classic prescription originally reported in the book “Su Wen Bing Ji Qi Yi Bao Ming Ji” It is a common therapeutic compound for treating colitis and CAC accompanied with spleen deficiency and qi stagnation syndrome. Atractylenolide II (the main component of Rhizoma Atractylodis) has an anti-proliferative effect on digestive tumors [14]

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