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, Materials and methods: We evaluated the cytotoxicity of ant imicrotubule agents to seven human SCLC cell lines consisting of one cell l ine (SBC-3) established from a previously untreated patient as a representa tive of drug-sensitive cell line, three cell lines (SBC-2, SBC-4, and -7) d erived from treated patients as representatives es of intrinsic drug-resist ance cell lines, and three drug-resistant sublines (SBC-3/ADM, SBC-3/ETP, a nd SBC-3/CDDP) selected by continuous exposure of the SBC-3 cell line to in creasing concentrations of doxorubicin, etoposide, or cisplatin as represen tatives 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/E TP subline were highly resistant to paclitaxel, docetaxel, vinorelbine, vin cristine, vindesine, and vinblastine. However, an SBC-3/ADM subline was not fully cross-resistant to rhizoxin and an SBC-3/ETP subline was as sensitiv e to rhizoxin as an SBC-3 cell line. A cisplatin-resistant subline, SBC-3 / CDDP, showed no cross-resistance to the antimicrotubule agents. Conclusion: These results suggest that antimicrotubule agents are useful for SCLC, and rhizoxin may be particularly effective in the salvage treatment of refract ory or relapsed patients.