罗非昔布联合奥曲肽增强对胰腺癌生长的抑制作用

目的　探讨高选择性环氧合酶 2抑制剂———罗非昔布联合奥曲肽能否协同增强对人胰腺癌生长的抑制。方法　采用3 H 胸腺嘧啶核苷参入法了解这两种药物单独或联合应用对人胰腺癌细胞株BXPC 3DNA合成的影响 ,根据中效原理判断联合用药是否产生协同效应。观察这两种药物单用或联合应用对裸鼠人胰腺癌移植瘤生长的影响。结果　罗非昔布显著抑制胰腺癌细胞3 H 胸腺嘧啶核苷参入 ,药物浓度与3 H 胸腺嘧啶核苷参入值呈负相关 ,r=- 0 990 ,P <0 0 1。罗非昔布联合奥曲肽在多数效应范围内的合用指数小于 1,有协同作用。与对照组比较 ,罗非昔布或奥曲肽均能抑制裸鼠胰腺癌移植瘤的生长 ,但联合用药的抑瘤率(97 4 % )明显高于单用奥曲肽 (5 7 0 % )或罗非昔布(87 7% ) ,P <0 0 1。结论　罗非昔布联合奥曲肽可协同增强对人胰腺癌的生长抑制

Enhanced effects of combination of rofecoxib and octreotide on growth of human pancreatic cancer

AIM Most of pancreatic cancer expresses cyclooxygenase-2 (COX-2). The suppression of various kind of neoplasm by somatostatin was reported. We hypothesis that the combination of rofecoxib (high selective COX-2 inhibitors)and octreotide (somatostatin analog) may synergically enhance the inhibitive effects on growth of human pancreatic cancer as well as with less dosage or side effects due to the different mechanisms of anti-neoplasm behind both non-cytotoxitic agents. METHODS The proliferation of human pancreatic cancer cell line BXPC-3 was measured by 3H-thymidine incorporation into DNA. To determine the synergic effects of anti-neoplasm, the interaction between rofecoxib and octreotide on BXPC-3 cell was evaluated according to the median-response principle. We also assessed the effects of rofecoxib combined with octreotide on the growth of BXPC-3 cell xenografts in nude mice in vivo. RESULTS A dose-dependent inhibition (r=-0.990,P<0.01) of 3H-thymidine incorporation in BXPC-3 cell line treated with rofecoxib was observed. In the range of majority responses, the combination indexes for rofecoxib plus octreotide were less than 1 indicating synergic effects. The average volumes or weights of tumors in nude mice of three treatment groups were significantly lower than those of control group. The inhibition rate for pancreatic cancer xenografts in nude mice in the combination group (97.4%) was notably enhanced when compared with rofecoxib (87.7%) or octreotide group (57.0%), P<0.01. CONCLUSIONS The inhibitive effects on human pancreatic cancer were markedly improved by rofecoxib combined with octreotide when compared with either drug alone. These synergic results may be of potential therapeutic benefit to those patients with pancreatic cancer.