β-Tubulin Isoforms Related to Docetaxel Sensitivity in 2D and 3D Cultured TNBC Cell Lines

Abstract

Background/Aim: We previously reported that the half maximal inhibitory concentration (IC₅₀) values of cisplatin and epirubicin correlated in 13 triple-negative breast cancer (TNBC) cell lines between two-dimensional (2D) and three-dimensional (3D) culture methods. However, the IC50 values of docetaxel (DTX) did not correlate between the two culture methods. We hypothesized that this non-correlation is partly associated with differences in expression of the β-tubulin isoform, the target molecule of DTX and in morphology depending on the culture method. Materials and Methods: We investigated the expression levels of β-tubulin isoforms by real-time polymerase chain reaction and morphology of spheroid formation in the 13 TNBC cell lines cultured using the 2D and 3D culture methods. Results: Tubulin β class I (TUBB) expression levels were negatively correlated with the IC₅₀ value of DTX in the 2D culture method (R=−0.360), whereas tubulin β class IIa (TUBB2a) expression levels were positively correlated in the 3D culture method (R=0.398). There was no significant difference in the expression levels of β-tubulin isoforms between the 2D and 3D culture methods. The spheroids were classified morphologically into three types: round, mass, and grape-like. However, no clear association was found between DTX sensitivity and morphology. Conclusion: The non-correlation of the IC₅₀ values of DTX between the 2D and 3D culture methods does not appear to be due to the changes in β-tubulin isoforms. Morphology in the 3D culture method may play some role in drug sensitivity.