Sensitivity to Novel Platinum Compounds of Panels of Human Lung Cancer Cell Lines with Acquired and Inherent Resistance to Cisplatin

摘要: We have developed panels of human lung cancer cell lines with acquired and inherent resistance to cisplatin. Three parental lines, NCI-H69/P (small cell), COR-L23/P (large MOR/P (adenocarcinoma), were grown in increasing concentrations cisplatin over a period 6-9 months. This resulted the development sublines, H69/CPR, L23/CPR, MOR/CPR which 3- 8-fold resistant as determined by 6-day 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. None sublines showed significant change cellular glutathione content or sensitivity cadmium chloride (an indicator metallothionein content), although changes glutathione-S-transferase activity seen. The each cross-resistance melphalan. Cisplatin accumulation was unchanged 1.3-fold reduced 2.0-fold compared their respective parent lines. In panel 10 small there 16-fold range sensitivities been used examine between cisplatin, carboplatin, iproplatin, tetraplatin, series novel ammine/amine dicarboxylate platinum(IV) compounds. Whereas H69/CPR little no any other compounds, L23/CPR generally cross-resistant all them. whereas ranking carboplatin similar, compounds provided individual patterns sensitivity. There always wide among panel, ranging from 8- 28-fold. Among great potencies, two (JM273 JM274) being approximately 100-fold more potent than