Table 3

Inhibitory effects of paclitaxel and discodermolide on growth of human cancer cells

IC50(relative resistance)
Colon carcinomaOvarian carcinoma
ParentalPactitaxel resistant MDRParentalPaclitaxel resistant
SW620SW620AD-3001A9MDRβ-tubulin mutants
A2780AD1A9PTX101A9PTX22
nm
Paclitaxel0.28  ± 0.08/2260  ± 10/2 (930)1.4  ± 0.2/113900  ± 400/4 (2800)32  ± 8/7 (23)41  ± 5/10 (29)
Discodermolide2.8  ± 0.4/370  ± 10/3 (25)6.5  ± 1/7580  ± 200/3 (89)7.2  ± 0.7/3 (1.1)13  ± 3/6 (2.0)

The colon carcinoma parental line is SW620, and the paclitaxel-resistant line is SW620AD-300, which overexpresses P-glycoprotein, resulting in MDR (26). The ovarian carcinoma parental line, designated 1A9, was derived as a subclone of line A2780 (24). The line A2780AD overexpresses P-glycoprotein (25). Two resistant lines, designated 1A9PTX10 and 1A9PTX22, were derived by growing the parental cells in paclitaxel and verapamil. Both lines express modified β-tubulin polypeptides (20). See footnote 1 in the text for further details. IC50 is the drug concentration that inhibits cell growth by 50%, as measured by cell protein. Relative resistance is obtained by dividing the IC50 value of the resistant line by the IC50 value of the parental line. Values are presented as mean ± standard error. The number of independent determinations in each case is indicated after the virgule.