One of the major barriers to successful chemotherapy is development of resistance. A significant amount of fundamental and clinical data has been amassed suggesting that one of the major causes for resistance to taxanes is overexpression of the class III beta-tubulin (betaIII-tubulin) isotype. Correlation between betaIII-tubulin overexpression and taxane resistant tumors has been observed in several types of malignancies; breast cancer, non-small cell lung cancer and ovarian cancer [1]. Therefore, it is crucial to further investigate the possible role of betaIII-tubulin in tumor resistance. Understanding its role will help us in future drug research and drug design, as well as patient treatment.

To determine what role betaIII-tubulin plays in response to taxotere or ixabepilone treatment, I used MCF7 stably expressing enhanced green fluorescent protein-alpha-tubulin cells to study the effects of taxotere or ixabepilone after small interfering RNA mediated knockdown of betaIII-tubulin. I report suppressive effects of taxotere and ixabepilone in live interphase cells on microtubule dynamic instability. Taxotere suppressed the growth rate of microtubules in cells expressing reduced amounts of betaIII-tubulin with lower potency than it suppressed growth rate of microtubules in control siRNA-transfected (control transfected) cells. Ixabepilone on the other hand suppressed the shortening rate, rescue distance and dynamicity of microtubules more strongly in cells expressing reduced amounts of betaIII-tubulin than in control transfected cells.

We also found a weaker mitotic arrest by taxotere and ixabepilone in betaIII-tubulin knockdown cells compared to control transfected cells, but in a cell proliferation assay there was no difference in IC50 values for taxotere or ixabepilone between control transfected and betaIII-tubulin knockdown cells. These results show that betaIII-tubulin knockdown may reduce suppression of microtubule dynamic instability by taxotere and enhances the effects of ixabepilone on suppression of microtubule dynamic instability; but in prolonged drug incubation, knockdown of betaIII-tubulin has no effect on taxotere or ixabepilone sensitivity.