摘要
探讨罗非昔布联合奥曲肽能否增强对胃癌生长的抑制及初步机制。采用3H 胸腺嘧啶掺入观察药物对胃癌细胞DNA合成的影响。应用中效原理分析两药联用的效应性质。观察罗非昔布联合奥曲肽对人胃癌裸鼠原位移植瘤生长的作用。免疫组化检测胃癌PCNA表达 ,TUNEL法检测细胞凋亡。罗非昔布联合奥曲肽在体外能协同抑制胃癌细胞的DNA合成。罗非昔布对胃癌的抑瘤率为 89 7% ,显著低于联合组 (98 8% ) (P <0 0 1)。罗非昔布使体外或体内胃癌细胞PCNA指数下降 6 3%或 4 3% ,联合奥曲肽后下降 83 3%或 79 3% (P <0 0 5 )。罗非昔布组胃癌移植瘤细胞凋亡指数为 (4 6 6 0± 3 4 2 ) % ,显著高于对照组 (8 5 6± 2 34) % (P <0 0 1) ,显著低于联合组 (78 2±6 5 ) % (P <0 0 1)。罗非昔布联合奥曲肽通过增加胃癌细胞凋亡及抑制细胞增殖从而增强对胃癌生长的抑制。
The study was aimed to know whether rofecoxib combined with octreotide inhibite growth of gastric cancer. Proliferation of gastric cancer cell line affected with rofecoxib or octreotide was determined by 3H-thymidine ribotide incorporation. To determine the synergic effects of anti-neoplasm, the interaction between rofecoxib and octreotide on SGC-7901 cell was evaluated according to the median effect plot. The expression of proliferating cell nuclear antigen (PCNA) of gastric adenocarcinoma cells was detected by immunocytochemistry. The TdT-mediated dUTP nick end labeling assay was used to detect the apoptosis. After xenografts of human gastric cancer were implanted orthotopically in stomach, nude mice were administrated with rofecoxib plus octreotide for 8 weeks. Combination of rofecoxib and octreotide presented synergistic effect (combination index <1) in majority of responses. The inhibitory rate for xenografts in nude mice was 89.7% in rofecoxib group. However, rofecoxib combined with octreotide was able to enhance inhibitory rate of tumor to 98.8%. Futhermore, the combination of rofecoxib and octreotide greatly increased the apoptosis index (78.20%±6.45%) of the xenografts when compared with rofecoxib alone(46.60%±3.42%), P<0.001. Moreover, the combination therapy greatly decreased the PCNA index of SGC7901 either in vitro or in vivo. Combination of rofecoxib and octreotide significantly enhanced the anti-proliferation effect in gastric adenocarcinoma. This result may be of potential therapeutic interest.
出处
《基础医学与临床》
CSCD
北大核心
2004年第3期277-281,共5页
Basic and Clinical Medicine
基金
国家自然科学基金 (30 170 4 18)
