RNA-seq and In Vitro Experiments Reveal the Protective Effect of Curcumin against 5-Fluorouracil-Induced Intestinal Mucositis via IL-6/STAT3 Signaling Pathway.

Xuan-Ying Wang,Qing-Hua Yao,Bo Zhang,Lu Xu,Yi-Jie Wang,Bi-Yu Cai,Yi Lu,Kai Wang

doi:10.1155/2021/8286189

Abstract

Although first-line chemotherapy drugs, including 5-fluorouracil (5-FU), remain one of the major choice for cancer treatment, the clinical use is also accompanied with dose-depending toxicities, such as intestinal mucositis (IM), in cancer patients undergoing treatment. IM-induced gastrointestinal adverse reactions become frequent reason to postpone chemotherapy and have negative impacts on therapeutic outcomes and prognosis. Various studies have evidenced the anticancer role of curcumin in many cancers; except for this effect, studies also indicated a protective role of curcumin in intestinal diseases. Therefore, in this study, we investigated the effect of curcumin on inflammation, intestinal epithelial cell damage in an IM model. 5-FU was used to induce the model of IM in intestinal epithelial cells, and curcumin at different concentrations was administrated. The results showed that curcumin efficiently attenuated 5-FU-induced damage to IEC-6 cells, inhibited the levels of inflammatory cytokines, attenuated the 5-FU-induced inhibition on cell viability, and displayed antiapoptosis effect on IEC-6 cells. Further RNA-sequencing analysis and experiment validation found that curcumin displays its protective effect against 5-FU-induced IM in intestinal epithelial cells by the inhibition of IL-6/STAT3 signaling pathway. Taken together, these findings suggested that curcumin may be provided as a therapeutic agent in prevention and treatment of chemotherapy-induced IM.

Highlights

Chemotherapy remains one of the major strategies for cancer treatment, with the ability of inhibiting cancer cell growth and metastasis to a certain extent
Intestinal mucositis (IM) is a major adverse effect induced by chemotherapeutic agents, such as 5-fluorouracil (5-FU), in cancer patients undergoing treatment [2]. 5-FU is a commonest first-line systemic chemotherapy drug used to fight against numerous types of cancers, colorectal cancer [3,4,5]
In the curcumin-treated groups, it could be observed that the coincubation with curcumin at 10 and 20 μmol/L for 24 h and 48 h significantly improved the IEC-6 cell viability, compared with the 5-FU group

Summary

Introduction

Chemotherapy remains one of the major strategies for cancer treatment, with the ability of inhibiting cancer cell growth and metastasis to a certain extent. Intestinal mucositis (IM) is a major adverse effect induced by chemotherapeutic agents, such as 5-fluorouracil (5-FU), in cancer patients undergoing treatment [2]. Except for its anticancer effect, studies indicated a protective role of curcumin in alimentary system. Curcumin can protect human intestinal epithelial cell from inflammatory damage and cell apoptosis induced by IFN-γ, indicated the preventive role of curcumin in intestinal damage [14]. Zhang et al report that curcumin displays a protective role in intestinal inflamed rat, and this effect is realized by inhibiting cell apoptosis and JAK/STAT pathways [15]. In this study, we investigated the effect of curcumin on intestinal epithelial cell damage and inflammation induced by 5-FU. The discovered protective properties of curcumin in this study may provide a possible option in prevention and treatment 5-FU-induced IM

Material and Methods

Results

Discussion