Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21

• Published in: International journal of immunopathology and pharmacology 2018-03, Vol.32, p.2058738418814341
• Main Authors: Zhu, Genglong, Liu, Xialei, Li, Haijing, Yan, Yang, Hong, Xiaopeng, Lin, Zhidong
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell viability; Down-Regulation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Hep G2 Cells; Humans; Kaempferols - pharmacology; Kinases; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; MicroRNAs; MicroRNAs - metabolism; Neoplasm Invasiveness - pathology; Original; Phosphatidylinositol 3-Kinase - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Up-Regulation - drug effects
• ISSN: 0394-6320; 2058-7384
• DOI: 10.1177/2058738418814341

Liver cancer is one of the most common and lethal cancers in human digestive system, which kills more than half a million people every year worldwide. This study aimed to investigate the effects of kaempferol, a flavonoid compound isolated from vegetables and fruits, on hepatic cancer HepG2 cell proliferation, migration, invasion, and apoptosis, as well as microRNA-21 (miR-21) expression. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell proliferation was measured using 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. Cell apoptosis was assessed using Guava Nexin assay. Cell migration and invasion were determined using two-chamber migration (invasion) assay. Cell transfection was used to change the expression of miR-21. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze the expressions of miR-21 and phosphatase and tensin homologue (PTEN). Expression of key proteins involved in proliferation, apoptosis, migration, invasion, and phosphatidylinositol 3-kinase/protein kinase 3/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were evaluated using western blotting. Results showed that kaempferol significantly inhibited HepG2 cell proliferation, migration, and invasion, and induced cell apoptosis. Kaempferol remarkably reduce the expression of miR-21 in HepG2 cells. Overexpression of miR-21 obviously reversed the effects of kaempferol on HepG2 cell proliferation, migration, invasion, and apoptosis. Moreover, miR-21 negatively regulated the expression of PTEN in HepG2 cells. Kaempferol enhanced the expression of PTEN and inactivated PI3K/AKT/mTOR signaling pathway in HepG2 cells. In conclusion, kaempferol inhibited proliferation, migration, and invasion of HepG2 cells by down-regulating miR-21 and up-regulating PTEN, as well as inactivating PI3K/AKT/mTOR signaling pathway.