The aromatase inhibitor letrozole and inhibitors of insulin-like growth factor I receptor synergistically induce apoptosis in in vitro models of estrogen-dependent breast cancer

Table 3 Summary of altered cell cycle distribution in response to treatment with single agent or in combination

Cell line	Compound	Sub-G₁ (%)	G₁ phase (%)	S phase (%)	G₂/M phase (%)	Annexin/7-AAD (%)
MCF7Aro (24 hours)	-Δ4A	2.5	77.7	11.1	9.3	3.5
	+Δ4A	1.6	39.9	41.8	17.5	2.8
	AEW541 (92 nmol/l)	2.2	44.0	39.1	15.1	3.2
	Letrozole (445 nmol/l)	3.1	74.2	12.8	10.7	2.7
	AEW541 + Letrozole	2.4	78.4	10.1	9.5	2.3
T47D/Aro	-Δ4A	0.6	86.5	4.1	8.1	ND
	+Δ4A	0.6	77.9	10.1	10.7	ND
	AEW541 (3.3 μmol/l)	0.3	83.8	6.2	9.0	ND
	Letrozole (165 nmol/l)	0.4	84.2	6.5	8.3	ND
	AEW541 + letrozole	0.4	87.3	3.8	8.1	ND
MCF7/Aro (96 hours)	-Δ4A	6.2	64.8	4.9	24.4	23.7
	+Δ4A	1.8	65.3	13.0	20.4	5.8
	AEW541 (92 nmol/l)	2.6	59.0	14.8	23.9	5.5
	Letrozole (445 nmol/l)	3.3	59.0	14.1	24.0	11.2
	AEW541 + Letrozole	7.3	58.7	12.2	22.4	22.5
T47D/Aro (96 hours)	-Δ4A	3.9	77.9	4.8	11.9	ND
	+Δ4A	0.9	68.2	16.7	13.4	ND
	AEW541 (3.3 μmol/l)	4.4	71.0	12.6	10.7	ND
	Letrozole (165 nmol/l)	1.6	80.8	5.8	10.8	ND
	AEW541 + letrozole	5.0	77.2	4.3	11.7	ND

Steroid-deprived MCF7/Aro and T47D/Aro cells were treated for 24, 48, or 96 hours with either no androstenedione (Δ4A; -Δ4A), Δ4A in the presence of dimethyl sulfoxide (+Δ4A), or Δ4A in the presence of the indicated concentrations of compound. Cells were processed for fluoresence-activated cell sorting (FACS) using propidium iodide and AnnexinV/7-AAD staining, as described in the text. Percentage distribution of cells in each cell cycle phase and total Annexin V stained cells are shown. The percentage value corresponds to upper and lower right quadrants of FACS plots in Figure 4b. ND, not determined.

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