RRC ID 39294
Author Fujita M, Tsuchida T, Higashino K.
Title Effect of vesnarinone in combination with anti-cancer drugs on lung cancer cell lines.
Journal Anticancer Drugs
Abstract Vesnarinone, a quinolinone derivative which is used as an oral inotropic agent in the clinic, has recently also been shown to have anti-cancer activity. We have studied the anti-cancer effect of vesnarinone in combination with cisplatin, VP-16 (etoposide) and gemcitabine, against human lung cancer cell lines (PC-9 and Lu 134A) using the MTT assay and isobologram analysis. Simultaneously, by establishing two cisplatin-resistant sublines, i.e. PC-9/CDDP and Lu 134A/CDDP, we analyzed the cross-resistance between vesnarinone and cisplatin and the resistance-reversing effect of vesnarinone. Nuclear fragmentation, as the presumed mechanism of tumor cell growth inhibition, was further studied quantitatively using flow cytometric analysis. Combination of vesnarinone with the studied anti-cancer drugs had a synergic or additive inhibitory effect on both PC-9 and Lu 134A tumor cell growth. Neither decrease of the sensitivity to vesnarinone nor cross-resistance between vesnarinone and anti-cancer drugs was observed. On the contrary, vesnarinone showed a resistance-reversing effect. Both vesnarinone and the studied anti-cancer drugs could induce tumor cell apoptosis, but a definite correlation between nuclear fragmentation and the growth inhibitory effect was not established.
Volume 10(1)
Pages 119-27
Published 1999-1
DOI 10.1097/00001813-199901000-00015
PMID 10194555
MeSH Adenocarcinoma / drug therapy* Antineoplastic Combined Chemotherapy Protocols / pharmacology* Carcinoma, Small Cell / drug therapy* Cell Division / drug effects Cisplatin / administration & dosage Coloring Agents / chemistry DNA Fragmentation / drug effects Deoxycytidine / administration & dosage Deoxycytidine / analogs & derivatives Dose-Response Relationship, Drug Drug Resistance, Neoplasm Drug Screening Assays, Antitumor Etoposide / administration & dosage Flow Cytometry Humans Lung Neoplasms / drug therapy* Lung Neoplasms / pathology Quinolines / administration & dosage* Tetrazolium Salts / chemistry Thiazoles / chemistry Tumor Cells, Cultured
IF 1.869
Times Cited 5
Human and Animal Cells