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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 investigate the inhibitory effect of alcohol extract of Taxus chinensis on heterotopic xenografts of multidrug-resistant human gastric cancer in nude mice and the effect of glucosylceramide synthase (GCS). Methods Human nude mice bearing vincristine (VCR) gastric cancer SGC7901 (SGC7901 / VCR) were inoculated subcutaneously in the back of 50 BALB / c nude mice. Twenty-four nude mice with similar tumor size were selected after 2 to 3 weeks and divided into 6 groups according to random number table: model group, VCR group, low-dose (warm-low) (Warm-high) group, low-dose alcohol extract combined with VCR (warm low + VCR) group, high-temperature alcohol extract combined VCR (warm + VCR) group. The animals were dosed by their respective drugs and dosages for 14 consecutive days. After the last administration, the animals were sacrificed, the tumor tissues were taken and the tumor inhibition rate was calculated. The expression of GCS-mRNA in the xenografts was detected by RT-PCR. GCS protein expression level. Results Compared with the model group, the tumor weight of VCR + VCR group was significantly reduced, and the expression of GCS mRNA and protein in VCR group was significantly increased. The expression of GCS mRNA and protein in VCR group, V + VCR group and V + VCR group were significantly higher The expression of GCS mRNA and protein in the hypothermia + VCR group and the V + VCR group were significantly lower than those in the warm group (P <0.05). Conclusion The combination of alcohol extract and VCR can inhibit the growth of human gastric cancer xenograft in SGC7901 / VCR nude mice. The inhibition may be related to the reversal of resistance to VCR by xyloty inducing xenografts in human gastric cancer SGC7901 / VCR nude mice. The reversal effect may be through GCS pathway, to improve the sensitivity of tumor cells to VCR.