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  • Title: Combretastatin A-4 resistance in H460 human lung carcinoma demonstrates distinctive alterations in beta-tubulin isotype expression.
    Author: Wehbe H, Kearney CM, Pinney KG.
    Journal: Anticancer Res; 2005; 25(6B):3865-70. PubMed ID: 16309172.
    Abstract:
    Tubulin isotype distribution may play a role in the development of anti-cancer anti-tubulin drug resistance as well as in drug efficacy and specificity. Stepwise selection was used to establish non-small cell lung carcinoma (NSCLC) H460 cells resistant to combretastatin A-4 (CA4), paclitaxel or vinblastine. The results demonstrated that the rate of CA4 drug resistance development was slower than that for paclitaxel. Western analysis demonstrated alterations in total beta-tubulin and classes I, III and IV tubulin isotypes among the resistant H460 cell lines. Class III beta-tubulin was significantly altered in all resistant cell lines. Cells resistant to paclitaxel, a structural stabilizer of microtubules, exhibited an increased expression while cells resistant to CA-4 and vinblastine, structural destabilizers of tubulin, demonstrated a reduction of the same isotype. To our knowledge, this is the first demonstration of resistance development and of the corresponding tubulin isotype response for the combretastatins.
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