Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with
cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellular resistance to the class of MIAs known as microtubule-
stabilizing agents (MSA). The human
lung cancer cell line A549 was compared with two
drug-resistant daughter cell lines, a
taxol-resistant cell line (AT12) and an
epothilone B (EpoB)-resistant cell line (EpoB40). The
ovarian cancer cell line Hey was compared with two
drug-resistant daughter cell lines, an EpoB-resistant cell line (EpoB8) and an
ixabepilone-resistant cell line (Ixab80). All 2D DIGE results were validated by Western blot analyses. A variety of cytoskeletal and cytoskeleton-associated
proteins were differentially expressed in
drug-resistant cells. Differential abundance of 14-3-3σ,
galectin-1 and phosphorylation of
stathmin are worthy of further studies as candidate predictive
biomarkers for MSAs. This is especially true for
galectin-1, a β-
galactose-binding lectin that mediates
tumor invasion and
metastasis.
Galectin-1 was greatly increased in EpoB- and
ixabepilone-resistant cells and its suppression caused an increase in
drug sensitivity in both
drug-sensitive and -resistant Hey cells. Furthermore, the growth medium from resistant Hey cells contained higher levels of
galectin-1, suggesting that
galectin-1 could play a role in resistance to MSAs.