塞来昔布联合奥曲肽对人胃癌多药耐药细胞生长的影响  

Inhibitory Effects of Celecoxib Combined with Octreotide on Growth of Multidrug Resistant Human Gastric Cancer Cell Line SGC7901/ADR

作　　者：郑文斌[1] 王春晖[1] 强鸥[1] 唐承薇[1] 

机构地区：[1]四川大学华西医院人类疾病生物治疗教育部重点实验室,人类疾病相关多肽研究室,四川成都610041

出　　处：《癌症》2004年第12期1628-1632,共5页Chinese Journal of Cancer

基　　金：国家自然科学基金项目(No.30170418);四川省科技厅攻关项目(No.02SG011-066)~~

摘　　要：背景与目的:环氧合酶-2(cyclooxygenase,COX-2)抑制剂塞来昔布及奥曲肽(octreotide)均对肿瘤细胞有抑制作用,本研究旨在探讨塞来昔布及其与奥曲肽联合对人胃癌多药耐药细胞株SGC7901/ADR生长的影响。方法:塞来昔布组:塞来昔布浓度为1×10-4～1×10-8mol/L;奥曲肽组:奥曲肽浓度为1×10-5～1×10-9mol/L;合用组:塞来昔布在上述浓度范围内加1×10-6mol/L的奥曲肽;对照组:无血清RPMI-1640培养液。比较各实验组对SGC7901、SGC7901/ADR细胞生长的影响。采用3H-胸腺嘧啶核苷(3H-TdR)掺入法检测细胞的增殖;免疫细胞化学检测增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)的表达;DNA末端原位标记染色法(TUNEL法)及流式细胞仪检测细胞凋亡。结果:塞来昔布较对照组明显降低SGC7901/ADR细胞的3H-TdR掺入,掺入值分别为(471.3±79.7)cpm及(917.5±130.8)cpm,塞来昔布与奥曲肽联合应用时,3H-TdR掺入值较单独用药(220.0±19.7)cpm下降53.3%。两药联合对SGC7901/ADR细胞DNA合成的抑制效应与塞郑文斌,等.塞来昔布联合奥曲肽来昔布的浓度呈显著正相关(r=0.996,P<0.001)。单用塞来昔布或联合用药都能明显降低SGC7901/ADR细胞PCNA的表达。单用塞来昔布时SGC7901/ADR细胞凋亡率为32.9%,当其与奥曲肽合用。BACKGROUND &OBJECTIVE: Both cyclooxygenase-2 (COX-2) inhibitor a nd octreotide can inhibit growth of tumor cells. This study was to investigate i nhibitory effects of COX-2 inhibitor celecoxib alone, and celecoxib combined wi th octreotide on growth of multidrug resistant human gastric cancer cell line SG C7901/ADR. METHODS: Experimental groups:(1)celecoxib (1×10-4-1×10-8 mol/L); (2)octreotide (1×10-5-1×10-9 mol/L); (3)celecoxib (1×10-4-1×10-8 mol/ L) combined with octreotide (1×10-6 mol/L);(4)control group (RPMI-1640 medium without serum). The effects of all treatments on SGC7901 cells, and SGC7901/ADR cells were observed. Cell proliferation was measured by 3H-thymidine incorpora tion into DNA. The expression of proliferating cell nuclear antigen (PCNA) was d etected by immunocytochemistry. Cell apoptosis was measured by TdT-mediated dUT P nick end-labeling assay (TUNEL) and flow cytometry. RESULTS: 3H-thymidine in corporation into SGC7901/ADR cells treated with celecoxib [(471.3±79.7) cpm] wa s significantly lower than that of control group [(917.5±130.8) cpm](P< 0.05). When combined with octreotide, celecoxib presented lower 3H-thymidine incorpora tion [(220.0±19.7)cpm] than it alone with a 53.3%decrease. The concentration of celecoxib in combination group negatively related to synthesis of DNA in SGC 7901/ADR cells (r=0.996,P< 0.001). The expression of PCNA in either celecoxib gr oup or combination group markedly decreased. The apoptosis rates of SGC7901/ADR cells induced by celecoxib alone, and combination treatment were 32.9%, and 52. 5%. CONCLUSION: Celecoxib combined with octreotide may enhance inhibition of gr owth of multidrug resistant human gastric cancer cells. The mechanism may be rel ated with inhibiting DNA synthesis, and inducing apoptosis.

关 键 词：胃肿瘤 多药耐药 环氧合酶-2 塞来昔布 奥曲肽 

分 类 号：R735.2[医药卫生—肿瘤]