Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

Table 1 Determination of IC₅₀ and resistance index of different anticancer drugs (mean ± SD)

	IC50		Resistance index	IC50		Resistance index
	HepG2	HepG2/ADM		SMMC7721	SMMC7721/ADM
Adriamycin (mg/L)	0.0063 ± 0.0022	0.135 ± 0.053	21.43	0.0139 ± 0.008	0.266 ± 0.036	19.14
Fluorouracil (&mgr;mol/L)	1.114 ± 0.271	25.34 ± 2.38	22.75	0.689 ± 0.082	48.5 ± 2.57	70.39
Cyclophosphamide (mg/L)	2.902 ± 0.369	32.68 ± 4.962	11.26	2.315 ± 0.279	60.08 ± 4.93	25.95
Cisplatin (mg/L)	0.0527 ± 0.013	1.084 ± 0.0749	20.57	0.0483 ± 0.011	1.637 ± 0.172	33.89
Mitomycin (mg/L)	0.061 ± 0.017	1.085 ± 0.246	17.79	0.032 ± 0.013	0.644 ± 0.168	20.13
Vincristine (mg/L)	0.0093 ± 0.0035	0.086 ± 0.0098	9.25	0.006 ± 0.004	0.247 ± 0.023	41.16

Table 2 Cell cycle distribution of parental and MDR HCC cells (mean ± SD)

Cells (n = 5)	G0/G1	S	G2/M
hepG2	65.08 ± 1.61	18.32 ± 1.37	16.58 ± 0.65
hepG2/ADM	62.44 ± 1.77a	12.24 ± 1.21b	25.36 ± 2.12c
SMMC7721	71.12 ± 1.38	17.86 ± 1.91	11.02 ± 1.95
SMMC7721/ADM	67.8 ± 2.15a	23.6 ± 0.93b	8.62 ± 2.74a

^aP < 0.05,

^bP < 0.01,

^cP < 0.001 vs control cells.

Table 3 P-gp and MRP1 expression in MDR and parental cells (mean ± SD)

Cells (n = 5)	P-gp (%)	MRP1 (%)
HepG2	0.88 ± 0.05	0.93 ± 0.15
HepG2/ADM	8.92 ± 0.22a	0.9 ± 0.18
SMMC7721	1.74 ± 0.25	1.21 ± 0.35
SMMC7721/ADM	7.37 ± 0.26a	0.79 ± 0.02

^aP < 0.001 vs parental cells.