RRC ID 57757
著者 Li M, Cui ZG, Zakki SA, Feng Q, Sun L, Feril LB Jr, Inadera H.
タイトル Aluminum chloride causes 5-fluorouracil resistance in hepatocellular carcinoma HepG2 cells.
ジャーナル J Cell Physiol
Abstract Chemoresistance is one of the major obstacles in chemotherapy-based hepatocellular carcinoma (HCC) intervention. Aluminum (Al) is an environmental pollutant that plays a vital role in carcinogenesis, tumorigenesis, and metastasis. However, the effect of Al on chemoresistance remains unknown. 5-Fluorouracil (5-FU) is a widely used antitumor drug. Therefore, we investigated the effects of aluminum chloride (AlCl3 ) on the chemoresistance of HepG2 cells to 5-FU and explored the underlying mechanisms of these effects. The results demonstrated that AlCl3 pretreatment attenuated 5-FU-induced apoptosis through Erk activation and reversed 5-FU-induced cell cycle arrest by downregulating p-Chk2Thr68 levels. In addition, AlCl3 markedly increased the levels of proteins associated with cell migration, such as MMP-2 and MMP-9. Further investigation demonstrated that an Erk inhibitor (U0126) reversed the AlCl3 -induced decrease in apoptosis, enhancement of cell cycle progression, promotion of cell migration, and attenuation of oxidative stress. In summary, AlCl3 induced chemoresistance to 5-FU in HepG2 cells. The present study suggests a potential influence of AlCl3 on 5-FU therapy. These findings may help others to understand and properly address the resistance of HCC to chemotherapeutic agents.
巻・号 234(11)
ページ 20249-20265
公開日 2019-11-1
DOI 10.1002/jcp.28625
PMID 30993729
MeSH Aluminum Chloride / pharmacology* Apoptosis / drug effects Carcinoma, Hepatocellular / drug therapy* Cell Cycle Checkpoints / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Down-Regulation / drug effects Drug Resistance, Neoplasm / drug effects* Fluorouracil / pharmacology* Gene Expression Regulation, Neoplastic / drug effects Hep G2 Cells Humans Liver Neoplasms / drug therapy* Oxidative Stress / drug effects Signal Transduction / drug effects
IF 4.522
引用数 1
リソース情報
ヒト・動物細胞 Hep G2(RCB1886)