Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells

Table 1 Tunicamycin-induced sensitization of UWOV2 ovarian carcinoma cells to various antineoplastic drugs

Drug	Alone**		Combination with TM**		Potency ratio^§ (95 % CI; p^‡‡)	Isobolar analysis of drug combinations^¶
	EC ₅₀ *	95 % CI ^‡	EC ₅₀ *	95 % CI		Index (I _x ) ^\|,∫	Interpretation
DXR	3.95	3.19 to 4.88	0.05	0.03 to 0.06	88 (62 to 126; p < 0.001)	0.15 ± 0.002 (n = 9)^†	Synergism
EXR	2.87	0.76 to 10.80	0.03	0.02 to 0.04	102 (29 to 354; p < 0.001)	0.23 ± 0.002 (n = 7)	Synergism
VCR	23.2	9.11 to 59.07	4.60	0.10 to 208	5 (0.14 to 177; p = 0.335)	0.54 ± 0.003 (n = 10)	Synergism
CDDP	4.07	3.68 to 4.51	0.24	0.13 to 0.44	17 (10 to 31; p < 0.001)	0.33 ± 0.002 (n = 9)	Synergism

*Data (μg/ml) are best-fit values obtained from non-linear regression analysis of the sigmoidal dose-response relation for each drug alone or in combination with a fixed concentration of 5 μg/ml TM. ^‡CI, confidence interval; ^§The potency ratio and associated 95% CI were computed using GraphPad QuickCalcs http://www.graphpad.com according to the method of Fieller [82] by subtracting the log EC₅₀ of drug in combination with TM from the log EC₅₀ of drug alone and back-transformation (antilog) of data; ^¶Analysis according to Chou and Talalay [81], using the CombiTool computer programme (version 2.001, http://www.imb-jena.de); I_x, the drug interaction index [73,79,80], ^|Values are geometric means ± ^†SEM (standard error of the mean) of multiple effect levels for each drug in the dose range 10^-4 to 10¹ μg/ml in the presence of a fixed concentration of 5 μg/ml TM; I_x < 1 ⇒ synergy; I_x = 1 ⇒ additivity and I_x > 1 ⇒ antagonism; ^‡‡Obtained from unpaired t-tests for the difference between log EC₅₀ for drug alone and drug in combination with TM; **One-way ANOVA for the differences in log EC₅₀ among treatment groups yielded p < 0.001 in all cases, except for VCR alone vs VCR in combination with TM which showed marginal significance: p = 0.061). ^∫Student t-tests to evaluate significant differences in I_x compared to a null hypothesized I_x value of 1, yielded p values < 0.001 in all cases.

ISSN: 1475-2867