Combined Treatment with Octreotide, Galanin and Serotonin in Gastrointestinal Malignancies

Triple therapy with octreotide, galanin and serotonin reduces the volume and weight of both rat and human colon carcinoma in xenografts. The reduction in tumour volume and weight seems to be caused by tumour necrosis, reduced proliferation and decreased expression of epidermal growth factor EGF of cancer cells, as well as induction apoptosis in cancer cells. Tumour necrosis has been suggested to be caused by induction of tumour ischemia due to a reduction in the tumour blood flow, which is caused by decreased incidence of tumour-feeding blood vessels and by constrictions of tumour feeding arterioles. The effects of single, double and triple therapy with octreotide, galanin and serotonin on rat colon cancer have shown that galanin alone reduced significantly the tumour-feeding blood vessels. The single and double treatment had a certain effect, but far from the triple treatment. Triple therapy had no apparent side effects. Triple therapy has equivalent antitumour and therapeutic efficacy as standard treatment with 5-fluorouracil/leucovorin. Triple therapy prolongs the survival rate of the mice bearing human pancreatic carcinoma and decreased both the volume and weight of tumours. However, the proliferation index and the labelling index for EGF were increased. It did not affect the apoptotic index, necrosis, or density of tumour blood vessels. In vitro investigations with single and double combinations of octreotide, galanin and serotonin have shown that single treatment with octreotide or serotonin reduces the number of viable cells and the proliferation index. Galanin increases the number of viable cells and the proliferation index. It has been concluded that treatment with a combination of octreotide, serotonin and galanin antagonist may be useful in clinical settings. The effect of triple therapy on gastric cancer is doubtful.