Potentiation of the anti-proliferative effects of anti-cancer drugs by octreotide in vitro and in vivo.
The somatostatin analogue octreotide (SMS 201-995) exerts potent anti-proliferative effects in a number of experimental cancer models. Here we report on the inhibitory effect of octreotide in combination with the chemotherapeutic agents mitomycin C, doxorubicin, 5-fluorouracil, or taxol on the growth of AR42J pancreatic cancer cells in vitro. The dose-dependent anti-proliferative effects of mitomycin C, doxorubicin and taxol were synergistically enhanced by octreotide. Combinations of octreotide and 5-fluorouracil resulted either in additive or, at high concentrations of the chemotherapeutic agent, in synergistic interactions. Combined treatment with doxorubicin and octreotide was also studied for time dependency and potential efficacy in tumour-bearing animals. Pretreatment (24 h) with doxorubicin resulted in clear synergy. However, pretreatment with octreotide 24 h prior to addition of doxorubicin resulted only in an additive interaction. It was shown in AR42J-tumour-bearing nude mice that the combination of doxorubicin and octreotide was well tolerated. Tumour growth was inhibited to 9% of controls, compared with 44% in the doxorubicin alone arm (day 14 of treatment). Our in vitro and in vivo interaction studies suggest that octreotide potentiates the effect of various chemotherapeutic agents in a synergistic or additive manner.