IC50(relative resistance) | |||||||
---|---|---|---|---|---|---|---|
Colon carcinoma | Ovarian carcinoma | ||||||
Parental | Pactitaxel resistant MDR | Parental | Paclitaxel resistant | ||||
SW620 | SW620AD-300 | 1A9 | MDR | β-tubulin mutants | |||
A2780AD | 1A9PTX10 | 1A9PTX22 | |||||
nm | |||||||
Paclitaxel | 0.28 ± 0.08/2 | 260 ± 10/2 (930) | 1.4 ± 0.2/11 | 3900 ± 400/4 (2800) | 32 ± 8/7 (23) | 41 ± 5/10 (29) | |
Discodermolide | 2.8 ± 0.4/3 | 70 ± 10/3 (25) | 6.5 ± 1/7 | 580 ± 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.