Gemcitabine is a DNA synthesis inhibitor (IC50s: 12, 18, 40, 92.7, 89.3 in Capan2, BxPC-3, Mia Paca-2, PANC-1, and PL-45 cells, respectively).

MTS assay demonstrates that Gemcitabine at 15 nM, indole-3-carbinol (I3C) at 50 μM and the combination does not affect hTERT-HPNE cell viability. However, treatment with Gemcitabine at 15 nM, I3C at 50 μM and the combination result in 31%, 19% and 72% cell death of BxPC-3 cells, respectively[1]. Gemcitabine inhibits the growth of HL-60 promyelocytic leukemia cells (LC50: 40 nM) [2]. Gemcitabine induces autophagy of SPC-A1 and A549 cells [3].

Gemcitabine can be administered via endotracheal spray in rats without marked toxicity with a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. The toxicity of Gemcitabine is lower via lung than oral administration at dosages of 2, 4, and 6 mg/kg [4]. Treatment of the LSL-KrasG12D/+; LSL-Trp53R172H; Pdx-1-Cre mice with either Gemcitabine (50 mg/kg, i.p.) or the combination DMAPT/Gemcitabine significantly increased the median survival time by more than 30 days compared to the placebo group (254.5 [P=0.015] or 255 days [P=0.018] vs. 217.5 days, respectively) [5].

The cytotoxic effect of gemcitabine was evaluated with the MTT assay. SPC-A1 or A549 cells were treated with gemcitabine (0.05–500 lM) for 24 h. Then, 10 ll of MTT (5 mg/ml in PBS) was added to each well and incubated for 4 h at 37 C. Then, the formazan crystals were solubilized with 200 ll DMSO. The absorbance at 570 nm was measured using an automatic multiwell spectrophotometer. The experiment was repeated four times for each group [3].

At 1 month of age, LSL-Kras G12D/+; LSL-Trp53 R172H; Pdx-1-Cre mice are randomized into treatment groups (placebo, DMAPT, Gemcitabine, DMAPT/Gemcitabine). Placebo (vehicle=hydroxylpropyl methylcellulose, 0.2% Tween 80 [HPMT]) and DMAPT (40 mg/kg body weight in HPMT) are administered by oral gastric lavage once daily. Gemcitabine (50 mg/kg body weight in PBS) is administered by intraperitoneal injection twice weekly. Mouse weight is monitored weekly. Treatment is continued until mice show signs of lethargy, abdominal distension or weight loss at which time they are sacrificed. Successful excision-recombination events are confirmed in the pancreata of mice by detecting the presence of a single LoxP site [5].

122111-03-9

C9H12ClF2N3O4

299.66

LY188011;吉西他滨盐酸盐;Gemzar;盐酸吉西他滨;LY 188011 hydrochloride;Gemcitabine HCl;Gemcitabine hydrochloride

[1]Ross DD, et al. Molecular effects of 2',2'-difluorodeoxycytidine (Gemcitabine) on DNA replication in intact HL-60 cells. Biochem Pharmacol. 1994 Oct 18;48(8):1619-30. [2]Huang C S, You X, Dai C, et al. Targeting Super‐Enhancers via Nanoparticle‐Facilitated BRD4 and CDK7 Inhibitors Synergistically Suppresses Pancreatic Ductal Adenocarcinoma[J]. Advanced Science. 2020: 1902926. [3]Gagnadoux F, et al. Safety of pulmonary administration of gemcitabine in rats. J Aerosol Med. 2005 Summer;18(2):198-206 [4]Wang H, et al. Enhanced efficacy of Gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrativenucleoside transporter 1. Anticancer Res. 2011 Oct;31(10):3171-80. [5]Yip-Schneider MT, et al. Dimethylaminoparthenolide and Gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer. BMC Cancer. 2013 Apr 17;13:194. [6]Wu HM, et al. Gemcitabine-Induced Autophagy Protects Human Lung Cancer Cells from Apoptotic Death. Lung. 2016 Dec;194(6):959-966. Epub 2016 Sep 7.

[1]Huang C S, You X, Dai C, et al. Targeting Super-Enhancers via Nanoparticle-Facilitated BRD4 and CDK7 Inhibitors Synergistically Suppresses Pancreatic Ductal Adenocarcinoma. Advanced Science. 2020, 7(7): 1902926 [2]Huang C S, You X, Dai C, et al. Targeting Super‐Enhancers via Nanoparticle‐Facilitated BRD4 and CDK7 Inhibitors Synergistically Suppresses Pancreatic Ductal Adenocarcinoma. Advanced Science. 2020: 1902926.

H2O:30 mg/mL (100 mM)
DMSO:6 mg/mL (20 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years