Circumvention of drug resistance in human non-small cell lung cancer in vitro by verapamil

• Published in: British journal of cancer 1987-10, Vol.56 (4), p.401-405
• Main Authors: Merry, S, Courtney, ER, Fetherston, CA, Kaye, SB, Freshney, RI
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Drug Resistance; Drug Screening Assays, Antitumor; Drug Synergism; Epidemiology; experimental-oncology; General aspects; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Medical sciences; Molecular Medicine; Oncology; Pharmacology. Drug treatments; Verapamil - pharmacology
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1987.214

The sensitivity of 7 human non-small cell lung cancer cell lines to each of 7 cytotoxic drugs was determined. None of the cell lines used in these experiments had been previously exposed to cytotoxic drugs in vitro. A pattern of cross-resistance (P less than 0.05) between the drugs adriamycin (ADR), vincristine (VC) and etoposide (VP16) was noted similar to that seen in other models. The calcium antagonist verapamil (6.6 microM) was shown to increase sensitivity (up to 29-fold) to ADR, VC or VP16 in 5 cell lines. For 2 of the cell lines (A549 and WIL) 2.2 microM verapamil increased VP16 cytotoxicity (up to 4-fold). Drug accumulation studies in 2 cell lines (A549 and SK-MES-1) showed that 6.6 microM verapamil increased intracellular levels of VC up to 4-fold with the greatest increase seen in the cell line (SK-MES-1) for which verapamil produced the greatest increase in cytotoxicity (10-fold). For ADR and VP16 increases in drug accumulation were smaller (up to 1.6-fold). Our data support a potential clinical role for verapamil in overcoming cytotoxic drug resistance in human lung cancer.