SMS 201.995 (Sandostatin) enhances in-vitro effects of 5-fluorouracil in colorectal cancer.
5-fluorouracil (5-FU) is still the most effective cytotoxic agent for the treatment of human colorectal cancer. Response rates, however, vary between 5-20%. One attempt to improve the effect of 5-FU is through biomodulation. We have previously found the somatostatin analogue, SMS 201.995 (Sandostatin, Sandoz), to inhibit both the in-vitro and in-vivo growth of some human colon cancer cell lines. It may act specifically by means of receptors on the surface of tumour cells, or by reducing the concentration of some growth factors. We report that, when 5-FU at 0.125 and 0.25 micrograms/ml was combined with SMS 201.995 at 10(-12) x 2 to 10(-8) x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved. Effects were measured using [3H]-thymidine uptake and by a colorimetric assay of cellular respiration (MTT, Promega, Sydney). SMS 201.995 alone has minimal inhibitory effects, whilst 5-FU alone shows inhibition as low as 39.6% of control. When 5-FU was then combined with SMS 201.995, a 10-30% inhibition occurred compared to the 5-FU control. The combination of 5-FU and SMS 201.995 may be a useful method of improving response to human colorectal cancer therapy.
Romani
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UNSW Department of Surgery, St George Hospital, Kogarah, Sydney, Australia.
Morris
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D000230:Adenocarcinoma / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003124:Colorimetry; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D015282:Octreotide / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015282:Octreotide; D005472:Fluorouracil; D013936:Thymidine