塞来昔布联合奥曲肽抑制胃癌转移的体内试验研究  

The inhibitive effects of celecoxib combined with octreotide on the metastasis of human gastric cancer in vivo

作　　者：黄茂涛[1] 陈志新[2] 魏兵[1] 张波[2] 王春晖[1] 黄明慧[3] 唐承薇[1] 

机构地区：[1]四川大学华西医院消化内科 [2]四川大学华西医院胃肠外科,成都610041 [3]四川大学华西医院人类疾病相关多肽实验室,成都610041

出　　处：《中华医学杂志》2006年第46期3255-3259,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30170418)

摘　　要：目的探讨塞来昔布联合奥曲肽能否抑制人胃癌细胞转移。方法75例胃癌患者被随机分为3组,每组25例。(1)对照组:术前不用任何抗肿瘤药物。(2)塞来昔布组:术前口服塞来昔布200mg/d,7d。(3)联合组:术前口服塞来昔布200mg/d(7d)+奥曲肽100μg/d(皮下注射7d)。免疫组化显示胃癌上皮性钙黏附蛋白(E-Cad)及基质金属蛋白酶(MMP)的表达,免疫印迹法定量检测胃癌组织MMP-2及MMP-9蛋白表达。术后胃癌组织经消化、免疫磁珠分离而得原代胃癌细胞,用改良的BodyenChamber膜侵袭系统比较3组术后胃癌细胞运动能力。结果胃癌组织E-Cad异常表达率在联合组(28·0%)及塞来昔布组(44·0%)明显低于对照组(56·0%,P<0·05)。3组MMP-2、MMP-9蛋白条带面积光密度积分值分别为99±20、260±15、314±11及89±13、180±13、241±12,联合组及塞来昔布组也都明显低于对照组(P<0·05)。联合组胃癌细胞迁移力较对照组低了38%(P<0·05)。结论塞来昔布联合奥曲肽有助于抑制胃癌细胞在人体内的转移。Objective To investigated if cyclooxygenase-2 （COX-2） inhibitor celecoxib in combination with somatostatin （SST） analog octreotide is able to inhibit the metastasis of human gastric cancer （GC） in vivo. Methods Seventy five patients with GC were randomly divided into 3 equal groups ： control group, taking no anti-tumor medicine before GC resection; celecoxib group, receiving celecoxib orally 200 mg/d for 7 days before surgery; and combination group, receiving celecoxib orally 200 mg/d and octreotide 100 μg injected subcutaneously for 7 days before operation. The resected specimens were studied for the expression of epithelial cadherin （E-Cad） and matrix metalloproteinase （MMP） by using immunohistochemical staining. MMP-2 and MMP-9 were also quantified with Western blotting. The GC cells from the resected gastric cancer specimens were isolated by immunomagnetic separation. Modified Boyden chamber membrane invasion culture system coated with Matrigel was used to observe the migration and invasion of the GC cells. Results The abnormal staining rates of E-Cad of GC tissue in the combination group and the celecoxib group were 28. 0% and 44. 0%, significantly lower than that in the control group （56. 0%, both P 〈 0. 05 ）. The grey level of MMP-2 and MMP-9 in the combination and celecoxib groups were （99 ± 20, 89 ±13 ） and （ 260 ± 15, 180 ± 13 ） respectively, both significantly lower than that of the control group [ （314 ± 11, 241 ± 12 ）, P 〈 0. 05 ]. The number of GC cells that penetrated the membrane was （2. 75 ±0. 58）/10^3 cells in the combination group, （2. 29 ±0. 58）/10^3 cells, the migration rate of the combination group was lower by 38% compared with that of the control group （ F = 6. 44, P 〈 0. 05 ） Conclusion The metastasis of human gastric carcinoma cells may be inhibited by the combinative treatment of celecoxib and octreotide.

关 键 词：胃肿瘤 肿瘤转移 奥曲肽 塞来昔布 

分 类 号：R735.2[医药卫生—肿瘤]