Modulating notch1 signaling pathway for treating neuroendocrine tumors
Methods and pharmaceutical compositions for treating or suppressing symptoms of neuroendocrine (NE) tumors comprising increasing the levels or activities of Notch1 protein or other components of the Notch1 signaling pathway of the cancer cells. Also disclosed are pharmaceutical compositions for the methods.
1. A method for inhibiting growth or neuroendocrine hormone production of a gastrointestinal (GI) carcinoid cancer cell which comprises an endogenous Notch1 gene, the method comprising increasing the level of expression product of the endogenous Notch1 gene of the GI carcinoid cancer cell, by contacting the GI carcinoid cancer cell with an effective amount of valproic acid (VPA), wherein growth or neuroendocrine hormone production of the GI carcinoid cancer cell is inhibited.
2. The method according to claim 1 , wherein the GI carcinoid cancer cell is an advanced stage GI carcinoid cancer cell.
3. A method for inhibiting in a mammal the growth or neuroendocrine hormone production of a gastrointestinal (GI) carcinoid cancer cell which comprises an endogenous Notch1 gene, wherein the method comprises administering an effective amount of valproic acid (VPA) to the mammal, wherein the level of expression product of the endogenous Notch1 gene of the GI carcinoid cancer cell is increased, or wherein the growth or neuroendocrine hormone production of the GI carcinoid cell is inhibited.
4. The method according to claim 3 , wherein the GI carcinoid cancer cell is an advanced stage GI carcinoid cancer cell.
5. The method according to claim 3 , wherein the mammal is treated with a daily intraperitoneal injection of VPA at a dosage of about 366 mg VPA/kg bodyweight.
6. The method according to claim 3 , wherein serum concentration of VPA in the mammal reaches a concentration of about 46 μg/ml two hours after intraperitoneal injection of VPA.