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

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 thein vivotumor 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.