Background Choroidal melanoma(CM)is a common form of primary ocular cancer in adults.It is reported that indomethacin has inhibitory effect on many tumor in vitro and in vivo,but whether it can inhibit the growth of CM has not been published. Objective This study was to investigate the anti-tumor activity of indomethacin on the growth of human CM OCM-1 cell xenografts in nude mice. Methods OCM-1 cells were subcutaneously implanted on 24 SPF female BALB/C.nuu nude mice to establish ectopic models of human CM.The nude mice with the tumor 5 mm were randomly divided into 4 groups:untreated group,normal saline solution(NS) group,indomethacin 1 ms/kg group,indomethacin 2 ms/kg group.The 1 mS/kg or 2 ms/kg indomethacin was intraperitoneally injected for 14 consecutive days in indomethacin 1 ms/kg group and indomethacin 2 me/kg group respectively.and 0.2 ml of 2%NS-DMSO was used at a same way in the NS group.No any agent was used as the untreated group.The volume and weight of implanted tumor as well as inhibitory rates of indomethaein on tumor were calculated.The expression of ki67 and survivin proteins were measured with immunohistochemistry,and the expression of survivin mRNA in CM was assessed by RT-PCR. ResuIts The tumor of indomethacin treatment group was reduced in volume and weight with a significant difference between treatment group and control group as well as indomethacin 1 ms/ks group and indomethacin 2 ms/kg group(P＜0.05).The inhibitory rate of indomethacin 1 ms/kg and 2 ms/kg for tumor was 22.86%,48.00%respectively.The prolifiration index (PI)of ki67 in these 4 groups were (76.73±3.34)%,(73.30±2.95)%,(55.97±2.24)%,(32.87±2.91)%respectively,and significant difference was found in PI between indomethacin 2 mg/kg group and untreated group or NS group(P＜0.05),but there was not significant difference between indomethacin 1 mg/kg and 2 ms/kg group(P＞0.05).Compared with the control group,the indomethacin treatment groups showed the decreased expression of survivin protein and mRNA,and significant difference was found between indomethaein 2 ms/kg group and untreated group or NS group(P＜0.05),however,no significant difference was found between indomethacin 1 mg/kg and 2 mg/kg group(P＞0.05). Conclusion Indomethacin inhibits the growth of CM in nude mice through inhibiting the expression of survivin in the tumor and accelerating cell apoptosis and inhibiting tumor cell proliferation.%背景 吲哚美辛能有效抑制多种肿瘤细胞的增生,但其对脉络膜黑色素瘤(CM)是否具有抑制作用尚不清楚.目的 探讨吲哚美辛对人CM细胞系OCM-1细胞裸鼠移植瘤生长的抑制作用.方法 将OCM-1细胞植入24只雌性裸鼠腋周皮下建立移植瘤模型,建模后5～6 d,待肿瘤长至5 mm大小时,将荷瘤鼠随机分为空白对照组、生理盐水组、吲哚美辛1 mg/kg组、吲哚美辛2 mg/kg组,按组每日腹腔注射相应的药物,连续用药2周,观察肿瘤生长情况.2周后处死动物,称量肿瘤重量并计算抑瘤率;应用免疫组织化学法检测各组动物肿瘤组织中ki67、survivin蛋白的表达;逆转录聚合酶链反应(RT-PCR)法分析各组小鼠肿瘤组织中survivin mRNA的表达.结果 吲哚美辛1 mg/kg组、吲哚美辛2 mg/kg组较空白对照组、生理盐水组CM肿瘤体积缩小、重量减轻,与空白对照组、生理盐水组比较差异均有统计学意义(P＜0.05);吲哚美辛2mg/kg组CM肿瘤的体积和重量均小于吲哚美辛1 mg/kg组,差异均有统计学意义(P＜0.05).吲哚美辛1 mg/kg组、吲哚美辛2 mg/kg组的抑瘤率分别为22.86%、48.00%,抑瘤率随吲哚美辛剂量的增加而升高.免疫组织化学染色及RT-PCR检测表明,吲哚美辛2 mg/kg组ki67增生指数、survivin蛋白及mRNA在肿瘤组织中的表达较空白对照组、生理盐水组明显下降,差异均有统计学意义(P＜0.05);但吲哚美辛1 mg/kg组与其他3组间上述3项指标的差异均无统计学意义(P＞0.05).结论 吲哚美辛可通过下调survivin的表达抑制OCM-1细胞的增生,从而抑制OCM-1裸鼠移植瘤的生长.
展开▼
