Characterisation of a vindesine-resistant human small-cell lung cancer cell line.
We established a vindesine-resistant (x 11.6) human small-cell lung cancer cell line (H69/VDS) by stepwise exposure of parent line H69 to vindesine. H69/VDS showed cross-resistance to taxol (x 10.1), vincristine (x 6.9) and colchicine (x 3.4) but not to doxorubicin, cisplatin or etoposide. There was no significant difference in intracellular [3H]-vincristine and doxorubicin accumulation between H69 and H69/VDS cells. The human mdr1 mRNA was not detected in either of the cell lines. These results indicated that H69/VDS did not express a typical multidrug resistant phenotype. Addition of 20 microM verapamil enhanced the growth inhibitory effect of vindesine on both H69/VDS (x 12.0) and H69 cells (x 3.8). The amount of total tubulin in H69/VDS cells was lower than that in the H69 parental cells. No significant increase was observed in the amount of total and polymerised tubulins of H69 cells. In H69/VDS cells, however, verapamil increased the amount of total tubulin to the level of parental cells, but decreased the amount of polymerised tubulin. Modulation of tubulin may play a role in the resistance to vindesine.
Pharmacology Division of National Cancer Center Research Institute, Tokyo, Japan.
S
S
Ohta
K
K
Nishio
S
S
Kubo
M
M
Nishio
T
T
Ohmori
T
T
Takahashi
N
N
Saijo
D000970:Antineoplastic Agents / Q000633:toxicity*; D015152:Blotting, Northern; D015153:Blotting, Western; D018288:Carcinoma, Small Cell; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002999:Clone Cells; D004351:Drug Resistance; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014404:Tubulin / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014751:Vindesine / Q000633:toxicity*
D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D014404:Tubulin; D014700:Verapamil; D014751:Vindesine