温郁金醇提物对多药耐药人胃癌裸鼠异位移植瘤的抑制及葡萄糖神经酰胺合成酶的影响  

Inhibitory Effect of Curcuma wenyujin Alcohol Extract on Ectopic Transplantation Tumor of Multidrug Re-sistant Nude Mice and Glucosylceramide Synthase

作　　者：宋淑萍[1] 蔡利军[1] 孟立娜[1] 

机构地区：[1]浙江中医药大学附属第一医院消化科,杭州310006

出　　处：《中国中西医结合杂志》2017年第7期853-857,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：浙江省教育厅科研项目(No.Y201119889);浙江省自然科学基金资助项目(No.LY16H290001)

摘　　要：目的探讨温郁金醇提物对多药耐药人胃癌裸鼠异位移植瘤的抑制及葡萄糖神经酰胺合成酶(glucosylceramide synthase,GCS)的影响。方法将人耐长春新碱(vincristine,VCR)胃腺癌细胞SGC7901(vincristine-resistant gastric cancer SGC7901 cells,SGC7901/VCR)接种于50只BALB/c裸鼠右侧背部皮下,建立荷瘤裸鼠模型,2~3周后选取瘤体大小相近的裸鼠36只,按随机数字表法分为6组:模型组,VCR组,温郁金醇提物低剂量(温低)组,温郁金醇提物高剂量(温高)组,温郁金醇提物低剂量联合VCR(温低+VCR)组,温郁金醇提物高剂量联合VCR(温高+VCR)组。各组动物按各自药物和剂量给药,连续14天,末次给药后处死动物,剖取瘤体组织,计算抑瘤率以及应用RT-PCR检测移植瘤中GCS-mRNA的表达,Western blot检测GCS蛋白表达水平。结果与模型组比较,温高+VCR组瘤重明显减轻,VCR组GCS mRNA及蛋白表达量明显增高,温高组、温低+VCR组以及温高+VCR组中GCS mRNA及蛋白表达量明显降低,温低+VCR组以及温高+VCR组中GCS mRNA及蛋白表达量均明显低于温高组(P<0.05)。结论温郁金醇提物联合VCR可抑制人胃癌SGC7901/VCR裸鼠异位移植瘤生长;抑制作用可能与温郁金逆转人胃癌SGC7901/VCR裸鼠异位移植瘤对VCR的耐药有关。逆转作用可能是通过GCS途径,提高了肿瘤细胞对VCR的敏感性。Objective To observe the inhibitory effect of Curcuma wenyujin Alcohol Extract （CWAE） on ectopic transplantation tumor of multidrug resistant （MDR） nude mice and glucosylceramide synthase （GCS）. Methods Human vincristine-resistant （VCR） gastric cancer SGC7901/VCR cells in 50 nude mice were inoculated subcutaneously from right back to establish tumor bearing nude mice model. Totally 36 nude mice with similar tumor volume were selected 2 or 3 weeks later. Then they were divided into 6 groups according to random number table, i.e., the model group, the VCR group, the low dose CWAE group （CWAEL）, the high dose CWAE group （CWAEH group）, the CWAEL ＋ VCR group, the CWAEH ＋VCR group. Mice in each group were administrated with corresponding medications for 14 successive days. They were sacrificed after the last medication. The tumor tissue was anatomized. The tumor inhibition rate was calculated, mRNA and protein expressions of GCS were detected by RT-PCR and Western Blot respectively. Results Compared with the model group, the tumor weight was obviously reduced in the CWAEH ＋VCR group; GCS expression was significantly increased in the VCR group; GCS expression was significantly decreased in the CWAEH group, the CWAEL ＋ VCR group, and the CWAEH ＋VCR group. GCS expression was significantly lower in the CWAEL ＋VCR group and the CWAEH ＋VCR group than in the CWAEH group. Conclusions CWAE combined VCR could inhibit the growth of ectopic transplantation tumor in nude mice. Curcuma wenyujin might reverse resistance effect of VCR for ectopic transplantation tumor in nude mice. The reverse effect might be achieved by improving the sensi- tivity of tumor cells to VCR through GCS.

关 键 词：多药耐药 葡萄糖神经酰胺合成酶 温郁金 胃癌 

分 类 号：R285.5[医药卫生—中药学]