Bafilomycin A1 inhibits the growth and metastatic potential of the BEL-7402 liver cancer and HO-8910 ovarian cancer cell lines and induces alterations in their microRNA expression

摘要

The vacuolar H⁺-ATPase (V-ATPase) is commonly highly activated in cancer cells and is a potential target of anti-cancer therapy. Bafilomycin A1 is a specific inhibitor of the c subunit of V-ATPase. In the present study, the effects of bafilomycin A1 on the BEL-7402 hepatocellular carcinoma and HO-8910 ovarian cancer cell lines were respectively studied. In addition, the bafilomycin A1-induced alterations in the mRNAs and microRNAs (miRNAs) in the cells were detected using microarray methods. The results demonstrated that the growth of the two cell lines was retarded and the metastatic potential was inhibited by bafilomycin A1. Transmission electron microscopy and assays of capsase-3 and −9 suggested that bafilomycin A1 induced apoptosis. Gene Ontology analysis of the microarrays of mRNA-miRNA integrity showed altered pathways following bafilomycin A1 treatment, including pathways regulating glucose or lipid metabolism, DNA repair or duplication and lysosomes. Quantitative polymerase chain reaction analysis confirmed that miR-923, miR-1246, miR-149*, miR-638 and miR-210 were upregulated and miR-99a, miR-181a-2* and miR-339-5p were downregulated following bafilomycin A1 treatment. The overlapped altered miRs may be effective targets for the two types of solid tumor, and may have potential for application to the treatment of other types of solid tumor.