Table 1.

Sequence-dependent effects of ATRA/FK228 on cytotoxicity of DOX in NB4 cells

	CI
ATRA/FK228 followed by DOX			ATRA/FK228/DOX			DOX followed by ATRA/FK228
	ED50	ED75	ED90	ED50	ED75	ED90	ED50	ED75	ED90
Trypan blue-positive cells, %	3.81	5.47	10.80	1.34	0.77	0.60	0.99	0.71	0.71
Annexin V-positive cells, %	2.07	2.40	2.94	0.68	0.52	0.42	0.97	1.08	1.27

ATRA (0.125, 0.25, and 0.5 mM) and FK228 (1.0, 2.0, and 3.0 nM) were given at a fixed ratio either 24 hours prior to DOX (8.5, 17.0, and 34.0 nM) treatment, simultaneously with DOX, or 24 hours after initiation of DOX treatment. Total time of DOX exposure was 72 hours in all experiments. Effects on cytotoxicity were determined by annexin V flow cytometry and by cell counts using trypan blue exclusion test. Numbers represent CI values obtained at the ED₅₀, ED₇₅, and ED₉₀. ED₅₀ indicates 50% effective dose.