Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

BMC Cancer

Table 2 Resistance factors and relative drug uptake for MCF-7 breast tumour cells selected for survival in increasing concentrations (doses) of chemotherapy drugs

ll Line	Treatment	Dose 8		Dose 9		Dose 10		Dose 11		Dose 12
		Resistance Factor	Relative Uptake	Resistance Factor	Relative Uptake	Resistance Factor	Relative Uptake	Resistance Factor	Relative Uptake	Resistance Factor	Relative Uptake
MCF-7_DOX-2	Doxorubicin	1.80	93%	2.48	46%*	3.59	37%**	42.5	37%**	27.8	33%***
	Epirubicin	0.84	95%	2.91	38%**	6.99	29%***	14.8	27%*	4.79	28%**
MCF-7_EPI	Doxorubicin	1.82	108%	39.2	17%***	130.8	13%***	391.6	13%***	203.4	19%***
	Epirubicin	1.05	114%	93.9	11%***	422.6	9%***	486.2	9%**	815.3	14%**
MCF-7_TAX-2	Paclitaxel	1.00	115%	19.9	16%***	119.2	10%***	156.3	3%***	535.2	2%***
	Docetaxel	0.67		8.19		25.4		37.5		72.6
MCF-7_TXT	Paclitaxel	1.35	77%	29.4	30%***	16.9	17%***	148	28%**	251	9%***
	Docetaxel	1.05		15.9		3.00		30.8		79.2

MCF-7 cells exhibiting progressive resistance to doxorubicin, epirubicin, paclitaxel, or docetaxel were obtained (MCF-7_DOX-2, MCF-7_EPI, MCF-7_TAX-2, and MCF-7_TXT cells, respectively). Drug sensitivity for each drug-resistant cell line and MCF-7_CC cells at that selection dose was measured using a clonogenic assay. Resistance factors were then calculated by dividing the IC₅₀ value for the drug-resistant cell lines by the IC₅₀ value for MCF-7_CC cells. Drug uptake into drug-resistant cell lines was also measured as described in Materials and Methods and expressed relative to uptake into MCF-7_CC cells. Statistical analyses were conducted to determine if the drug uptake in the resistant cells varied significantly from MCF-7_CC cells (* p < 0.05, ** p < 0.01 and *** p < 0.001).

ISSN: 1471-2407