In vitro evaluation of antimicrotubule agents in human small-cell lung cancer cell lines.
BACKGROUND
The improvement of treatment outcome of small-cell lung cancer (SCLC), and search for new effective drugs and to overcome drug-resistance are essential.


METHODS
We evaluated the cytotoxicity of antimicrotubule agents to seven human SCLC cell lines consisting of one cell line (SBC-3) established from a previously untreated patient as a representative of drug-sensitive cell line, three cell lines (SBC-2, SBC-4, and -7) derived from treated patients as representatives of intrinsic drug-resistance cell lines, and three drug-resistant sublines (SBC-3/ADM, SBC-3/ETP, and SBC-3/CDDP) selected by continuous exposure of the SBC-3 cell line to increasing concentrations of doxorubicin, etoposide, or cisplatin as representatives of acquired drug-resistant cell lines.


RESULTS
IC50 values for SBC-2, -3, -4, and -7 cells of antimicrotubule agents were markedly lower than those of doxorubicin, etoposide, and cisplatin. Both SBC-3/ADM and SBC-3/ETP subline were highly resistant to paclitaxel, docetaxel, vinorelbine, vincristine, vindesine, and vinblastine. However, an SBC-3/ADM subline was not fully cross-resistant to rhizoxin, and an SBC-3/ETP subline was as sensitive to rhizoxin as an SBC-3 cell line. A cisplatin-resistant subline, SBC-3/CDDP, showed no cross-resistance to the antimicrotubule agents.


CONCLUSIONS
These results suggest that antimicrotubule agents are useful for SCLC, and rhizoxin may be particularly effective in the salvage treatment of refractory or relapsed patients.
Ikubo
S
S
Second Department of Internal Medicine, Okayama University Medical School, Japan.
Takigawa
N
N
Ueoka
H
H
Kiura
K
K
Tabata
M
M
Shibayama
T
T
Chikamori
M
M
Aoe
K
K
Matsushita
A
A
Harada
M
M
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000627:therapeutic use; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy*; D018942:Macrolides; D008870:Microtubules / Q000187:drug effects*; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000627:therapeutic use; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D018942:Macrolides; D043823:Taxoids; D000077143:Docetaxel; D005047:Etoposide; D004317:Doxorubicin; C041443:rhizoxin; D017239:Paclitaxel; D002945:Cisplatin