Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism

Table 3 In vivo effect of RU-486, propranolol, and siRNA-induced down regulation of tumor IL-6 expression, on circulating levels of IL-6, corticosterone and NORA, hepatic GSH and metastases growth

	Treatment
	Physiological saline		RU-486		Propranolol		IL-6-siRNA
Metastases	Lung	Liver	Lung	Liver	Lung	Liver	Lung	Liver
Tumor IL-6 expression (-fold change)	1.0 ± 0.1	1.0 ± 0.2	0.4 ± 0.1^**	0.3 ± 0.15^**	0.6 ± 0.2^**	0.7 ± 0.15^*	0.15 ± 0.05^**	0.2 ± 0.1^**
Serum IL-6 (pg/ml)	355 ± 81	432 ± 69	123 ± 36^**	154 ± 49^**	206 ± 77^*	255 ± 60^**	107 ± 40^**	124 ± 33^**
Liver GSH (μmol/g of tissue)	4.5 ± 05	3.8 ± 0.4	6.8 ± 0.6^**	5.9 ± 0.5^**	6.2 ± 0.5^**	5.5 ± 0.5^**	7.3 ± 0.6^**	7.1 ± 0.5^**
Plasma NORA (ng/ml)	406 ± 65	447 ± 72	337 ± 59	412 ± 77	426 ± 68	394 ± 59	433 ± 67	360 ± 45^*
Plasma NORA (ng/ml)	7.9 ± 1.5	8.7 ± 1.4	7.3 ± 1.2	8.1 ± 1.6	7.5 ± 1.1	8.5 ± 1.7	8.2 ± 1.3	9.2 ± 1.6
Metastases volume (%)	6.4 ± 09	8.5 ± 1.2	4.0 ± 0.6^**	5.0 ± 0.7^**	4.9 ± 0.5^**	5.8 ± 0.9^**	3.0 ± 0.7^**	3.7 ± 0.8^**

RU-486 (20 mg/kg body wt.) [47] or propranolol (10 mg/kg body wt.) [48] were administered i.p. with daily frequency, starting 24 h after tumor cell inoculation. All measurements (see under Material and methods) were performed 7 days after tumor cell inoculation. Plasma levels of corticosterone and NORA were measured at 12 h (circadian time, see Figure 1). Metastases volume is indicated as the mean percentage of organ volume occupied by metastases. The data show mean values + S.D. for 9–10 different experiments. **P< 0.01, *P< 0.05 comparing each condition versus physiological saline-treated controls.

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