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

关键词:  UPLC-MS/MS  康莱特注射液  吉西他滨  胰腺癌

Key words:  UPLC-MS / MS  kanglaite injection  gemcitabine  pancreatic cancer

摘要:

目的 本研究旨在探究康莱特注射液(KLTi)增强吉西他滨抗胰腺癌药效与其提升吉西他滨(GEM)的肿瘤细胞内积累的相关性。方法 建立超高效液相色谱-串联质谱(UPLC-MS/MS)方法,用于检测胰腺癌细胞内吉西他滨及其代谢产物dFdU的含量。通过MTS实验评估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联合处理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与吉西他滨联合可显著提升胞内GEM含量。MTS实验显示联合用药组的IC50值显著低于GEM单独用药组。结论 KLTi可通过显著提升吉西他滨的胞内积累增强GEM的胰腺癌杀伤作用。

Abstract:

OBJECTIVE The purpose of this study was to investigate the correlation between Kanglaite injection (KLTi) enhancing the efficacy of gemcitabine against pancreatic cancer and its enhancement of gemcitabine (GEM) accumulation in tumor cells. METHODS An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS) method was established to detect the content of gemcitabine and its metabolite 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 time, and the combination of KLTi and gemcitabine 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 gemcitabine.