Combretastatin A-4 Resistance in H460 Human Lung Carcinoma Demonstrates Distinctive Alterations in β-Tubulin Isotype Expression

• Published in: Anticancer research Vol. 25; no. 6B; p. 3865
• Main Authors: H. WEHBE, C.M. KEARNEY, K.G. PINNEY
• Format: Journal Article
• Language: English
• Published: International Institute of Anticancer Research 01.11.2005
• ISSN: 0250-7005; 1791-7530

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 β-tubulin and classes I, III and IV tubulin isotypes among the resistant H460 cell lines. Class III β-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.