Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, 14214, USA.
Ciblage Thérapeutique en Oncologie, Faculté de médecine Lyon-sud, Université Lyon 1, 69921, Oullins, France.
AAPS J. 2018 Jun 27;20(5):80. doi: 10.1208/s12248-018-0235-4.
The pharmacodynamic interactions among trifluoperazine (TFP), gemcitabine (GEM), and paclitaxel (PTX) were assessed in pancreatic cancer cells (PANC-1). The phenothiazine TFP was chosen for its potential activity on cancer stem cells, while GEM and PTX cause apoptosis. Effects of each drug alone and in various combinations on cell growth inhibition of PANC-1 cells were studied in vitro to determine the drug-specific parameters and assess the nature of drug interactions. Joint inhibition (JI) and competitive inhibition (CI) equations were applied with a ψ interaction term. TFP fully inhibited growth of cells (I = 1) with an IC = 9887 nM. Near-maximum inhibition was achieved for GEM (I = 0.825) and PTX (I= 0.844) with an IC = 17.4 nM for GEM and IC = 7.08 nM for PTX. Estimates of an interaction term ψ revealed that the combination of TFP-GEM was apparently synergistic; close to additivity, the combination TFP-PTX was antagonistic. The interaction of GEM-PTX was additive, and TFP-GEM-PTX was synergistic but close to additive. The combination of TFP IC-GEM IC-PTX IC seemed optimal in producing inhibition of PANC-1 cells with an inhibitory effect of 82.1-90.2%. The addition of ψ terms to traditional interaction equations allows assessment of the degree of perturbation of assumed mechanisms.
在胰腺癌细胞（PANC-1）中评估了三氟拉嗪（TFP）、吉西他滨（GEM）和紫杉醇（PTX）之间的药效学相互作用。选择吩噻嗪 TFP 是因为它对癌症干细胞具有潜在的活性，而 GEM 和 PTX 则引起细胞凋亡。在体外研究每种药物单独和各种组合对 PANC-1 细胞生长抑制的影响，以确定药物的特异性参数并评估药物相互作用的性质。应用联合抑制（JI）和竞争抑制（CI）方程，并加入 ψ 相互作用项。TFP 完全抑制细胞生长（I=1），IC=9887 nM。GEM（I=0.825）和 PTX（I=0.844）接近最大抑制，IC=17.4 nM 用于 GEM 和 IC=7.08 nM 用于 PTX。相互作用项 ψ 的估计表明，TFP-GEM 组合显然是协同的；接近加性，TFP-PTX 组合是拮抗的。GEM-PTX 的相互作用是相加的，而 TFP-GEM-PTX 是协同的，但接近加性。TFP IC-GEM IC-PTX IC 的组合似乎是抑制 PANC-1 细胞的最佳组合，抑制作用为 82.1-90.2%。在传统的相互作用方程中添加 ψ 项可以评估对假定机制的干扰程度。
