Konjac glucomannan reverses multi‑drug resistance of HepG2/5‑FU cells by suppressing AKT signaling and increasing p53 expression

Chen,Bin; Xu,Xin; Zheng,Ke; Liu,Ling; Yu,Yijun; Xin,Ying

doi:10.3892/ol.2020.11790

Konjac glucomannan reverses multi‑drug resistance of HepG2/5‑FU cells by suppressing AKT signaling and increasing p53 expression

Authors:
- Bin Chen
- Xin Xu
- Ke Zheng
- Ling Liu
- Yijun Yu
- Ying Xin
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Affiliations: Department of Hepatobiliary Surgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310011, P.R. China, Department of Hepatopancreatobiliary Surgery, The Affiliated Hangzhou Hospital of Zhejiang University, Hangzhou, Zhejiang 310002, P.R. China, Thyroid and Breast Surgery Department, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310006, P.R. China
Published online on: July 1, 2020 https://doi.org/10.3892/ol.2020.11790
Pages: 2105-2112
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The multi‑drug resistance (MDR) of cancer cells, including 5‑fluorouracil (5‑FU) resistance, has been a serious problem for patients with cancer. The present study aimed to investigate the reversal effects of konjac glucomannan on multi‑drug resistance of HepG2/5‑FU cells. In the present study, MTT assay was used to investigate the effects of 5‑FU and konjac glucomannan (KGM) on the viability of HepG2/5‑FU cells. Reverse transcription‑quantitative PCR and western blotting were performed to determine the effects of 5‑FU and KGM on the expression of MDR‑associated genes including MDR1 and P‑glycoprotein 1 (P‑gp 1), and to analyze the effects of 5‑FU and KGM on the levels of cell proliferation‑related genes, including cyclin A, cyclin B1 and CDK2, and apoptosis‑related genes, including caspase‑3, Bax and BCL‑2. Annexin V/propidium iodide staining was performed to determine the apoptotic rate of HepG2/5‑FU. Furthermore, the xenograft tumor model was established in nude mice to investigate the in vivo tumor growth by detecting tumor size, volume and tumor weight. KGM significantly decreased the viability of HepG2/5‑FU cells in the presence of 5‑FU. KGM downregulated the mRNA and protein expression of MDR and P‑gp, and inhibited the mRNA and protein expression of cyclin A, cyclin B1 and CDK2. In addition, KGM significantly suppressed BCL‑2 expression and increased the expression of cleaved caspase‑3 and Bax, resulting in a higher apoptotic rate of HepG2/5‑FU cells. Furthermore, KGM suppressed AKT phosphorylation and upregulated p53 expression. Notably, KGM significantly inhibited the growth of HepG2/5‑FU in nude mice. KGM may be a promising agent against the resistance of HepG2/5‑FU cells to 5‑FU by suppressing AKT signaling and increasing p53 expression.

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