康莱特注射液增强吉西他滨胞内积累促胰腺癌细胞杀伤的研究

    Kanglaite Injection Enhanced the Anti-pancreatic Cancer Cell Efficacy of Gemcitabine by Promoting the Drug Intraceullar Accumulation

    • 摘要:
      目的 探究康莱特注射液(Kanglaite injection,KLTi)增强吉西他滨(gemcitabine,GEM)抗胰腺癌药效与其提升GEM在肿瘤细胞内积累的相关性。
      方法 建立UPLC-MS/MS检测胰腺癌细胞内GEM及其代谢产物2’,2’-二氟-2’-脱氧尿苷(2’,2’-difluoro-2’-deoxyuridine,dFdU)含量的方法。通过MTS试验评估KLTi与GEM联合使用对胰腺癌细胞增殖的抑制作用,计算GEM在不同处理条件下的半数抑制浓度(IC50)和两药协同效应指数,探究胞内GEM与其无活性代谢产物dFdU的含量与IC50的相关性。
      结果 成功建立UPLC-MS/MS检测胞内GEM及dFdU含量的方法。与GEM单独处理相比,KLTi与GEM联用显著增加了胰腺癌细胞内GEM的含量。GEM单独处理胰腺癌细胞时,胞内GEM含量随时间呈下降趋势,KLTi与GEM联用显著提升胞内GEM含量。MTS试验显示联合用药组的IC50值显著低于GEM单独用药组。
      结论 KLTi可通过显著提升GEM的胞内积累,增强GEM的胰腺癌杀伤作用。

       

      Abstract:
      OBJECTIVE To investigate the correlation between Kanglaite injection(KLTi) enhancing the efficacy of gemcitabine(GEM) against pancreatic cancer and its enhancement of GEM accumulation in tumor cells.
      METHODS A UPLC-MS/MS method was established to detect the content of GEM and its metabolite 2’,2’-difluoro-2’-deoxyuridine(dFdU) in pancreatic cancer cells. The inhibitory effect of KLTi combined with GEM on the proliferation of pancreatic cancer cells was evaluated by MTS assay. The half inhibitory concentration(IC50) of GEM under different treatment conditions and the synergistic effect index of the two drugs were calculated to explore the correlation between the content of intracellular GEM and its inactive metabolite dFdU and IC50.
      RESULTS The UPLC-MS/MS method for the detection of intracellular GEM and dFdU was successfully established. Compared with GEM alone, the combination of KLTi and GEM significantly increased the content of GEM in pancreatic cancer cells. When pancreatic cancer cells were treated with GEM alone, the intracellular GEM content decreased with the time, while the combination of KLTi and GEM significantly increased the intracellular GEM content. MTS assay showed that the IC50 value of the combination group was significantly lower than that of the GEM alone group.
      CONCLUSION KLTi can enhance the killing effect of GEM on pancreatic cancer by significantly increasing the intracellular accumulation of GEM.

       

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