Chen T B, Huzak M, Macura S, Vuk-Pavlović S
Department of Oncology, Mayo Clinic, Rochester, MN 55905.
Cancer Lett. 1994 Oct 28;86(1):41-51. doi: 10.1016/0304-3835(94)90178-3.
To examine if preferential retention of somatostatin analogues observed in some tumors might be used for modulation of effects of cancer drugs by co-treatment with long acting somatostatin analogues, the effects of somatostatin analogue octreotide on the kinetics of 5-fluorouracil (FUra) and 5-fluorouridine (FUrd) metabolism were studied by 19F NMR spectroscopy in multicell tumor spheroids comprised of human colon HT-29 adenocarcinoma cells. Octreotide stimulated the rate of formation of fluorouridinephosphates in FUra-treated cells, but inhibited this rate in FUrd-treated cells. Other elements of fluoropyrimidine metabolism were also altered by co-incubation with octreotide. A flow cytometric analysis indicated that FUra and FUrd arrested cells in the S phase, but co-treatment with octreotide almost eliminated the S-phase cells and induced the appearance of DNA fragments. These observations raise the possibility that somatostatin analogues can be used for specific modulation of fluoropyrimidine effects in tumors bearing somatostatin receptors.
为了研究某些肿瘤中观察到的生长抑素类似物的优先保留是否可用于通过与长效生长抑素类似物联合治疗来调节抗癌药物的效果，利用19F核磁共振波谱技术，在由人结肠HT - 29腺癌细胞组成的多细胞肿瘤球体中，研究了生长抑素类似物奥曲肽对5 - 氟尿嘧啶（FUra）和5 - 氟尿苷（FUrd）代谢动力学的影响。奥曲肽刺激了FUra处理细胞中氟尿苷磷酸盐的形成速率，但抑制了FUrd处理细胞中的这一速率。与奥曲肽共同孵育也改变了氟嘧啶代谢的其他环节。流式细胞术分析表明，FUra和FUrd使细胞停滞在S期，但与奥曲肽联合治疗几乎消除了S期细胞并诱导了DNA片段的出现。这些观察结果提示，生长抑素类似物可用于对表达生长抑素受体的肿瘤中氟嘧啶效应进行特异性调节。
