塞来昔布联合卡培他滨对裸鼠人肝癌模型中肿瘤细胞增殖与凋亡的影响_临床医学论文.docVIP

塞来昔布联合卡培他滨对裸鼠人肝癌模型中肿瘤细胞增殖与凋亡的影响_临床医学论文 塞来昔布联合卡培他滨对裸鼠人肝癌模型中肿瘤细胞增殖与凋亡的影响_临床医学论文 作者：黄新余，王洪成，潘烨，戚大川，艾开兴，郑起 【摘要】 目的 研究环氧化酶-2抑制剂塞来昔布(Celecoxib)和化疗药物卡培他滨(Capecitabine)对裸鼠人肝癌模型中肿瘤细胞增殖与凋亡的影响。方法 建立LIC-D35裸鼠人肝癌模型，成瘤后40只裸鼠随机分成4组即对照组、塞来昔布组、卡培他滨组、联合用药组(卡培他滨与塞来昔布)。观察肿瘤大小，计算抑瘤率;采用RT-PCR方法观察肿瘤中COX-2的mRNA表达，并应用免疫组化法Ki-67检测肿瘤细胞增殖水平、末端脱氧核苷转移酶标记法(TUNEL)检测凋亡细胞。结果 对照组、塞来昔布组、卡培他滨组、联合组瘤体体积分别为(3 880±438)mm3、(3 374±465)mm3、(1 859±362)mm3和(981±197)mm3;塞来昔布组、卡培他滨组、联合用药组抑瘤率分别为15%、45%和71%。四组中Ki-67阳性率分别为46%、32%、25%和11%;肿瘤细胞凋亡指数DI分别为8%、22%、27%和38%;塞来昔布组、联合组肿瘤组织中COX-2 mRNA表达显著低于对照组和卡培他滨组(0.01)。结论 塞来昔布可显著抑制裸鼠人肝癌模型中肿瘤细胞COX-2 mRNA表达，抑制肿瘤细胞Ki-67表达，诱导肿瘤细胞凋亡。与卡培他滨联合应用可提高抗肿瘤效果。 【关键词】 环氧化酶-2抑制剂;裸鼠;肝肿瘤 　　[Abstract] Objective To evaluate the effect of celecoxib combined with capecitabine on proliferation and apoptosis of hepatocellular carcinoma in nude mice.Methods LIC-D35 liver tumors were orthotopically implanted in 40 nude mice and divided randomly into 4 groups:the control group(A)，the celecoxib group(B)，the capecitabine group(C)and the celecoxib combined with capecitabine group(D).Results Tumor volume was(3 880±438)mm3，(3 374±465)mm3，(1 859±362)mm3，(981±197)mm3 in the control，celecoxib，capecitabine and combined group，respectively.The rate of tumor inhibition was 15% in the celecoxib group，45% in the capecitabine group and 71% in the combined group.Immunohistochemical assays for tumor proliferation(Ki-67)showed the tumor cell proliferation Ki-67 positive rate was 46%,32%,25%，11% respectively and apoptosis index(TUNEL)was 8%，22%，27%，38%，respectively.The expression of COX-2 mRNA by RT-PCR method in celecoxib group and combined group showed it was highly suppressed compared with the control group and capecitabine group.Conclusion Celecoxib can suppress the expression of COX-2 mRNA of tumors orthotopic implanted in nude mice，it reduce proliferation and induce apoptosis of tumor cell;By combine with capecitabine，it can improve its anti-tumor activities. 　　[Key words] COX-2 inhibitor;nude mice;hepatocellular