化合物信息

Description

Cancer

Description

Gemcitabine Hydrochloride (Gemzar) is a DNA synthesis inhibitor with IC50 of 50 nM, 40 nM, 18 nM and 12 nM in PANC1, MIAPaCa2, BxPC3 and Capan2 cell lines, respectively.

Targets

IC₅₀

In Vitro

Gemcitabine induced NF-κB activity in BxPC-3, PANC-1, and MIA PaCa-2 cells and decreased the level of the NF-κB inhibitor IκBα in BxPC-3 and PANC-1 cells. Treatment of BxPC-3 cells with low dose Gemcitabine for 48 hours results in a dose-dependent increase in NF-κB binding. In contrast, NF-κB DNA binding is decreased in BxPC-3 cells treated with the higher Gemcitabine doses for 48 h; however, 24-h treatment with these higher doses increases NF-κB binding in BxPC-3 cells ^[2]

In Vivo

Intratumoral NF-κB activity is significantly elevated (1.3- to 1.8-fold) in the Gemcitabine-treated mice compared to the PBS-treated mice, suggesting that Gemcitabine also induces NF-κB activation. ^[2]

Clinical Trials

Gemcitabine plus PEGPH20 has entered in a phase II clinical trial in the treatmentof the stage IV pancreatic cancer.

Features

Gemcitabine has been used for pancreatic cancer as the most effective anticancer drug.

Description

The combination of P276 (a CDK inhibitor) and Gemcitabine results in a dose- and time-dependent inhibition of proliferation and colony formation of pancreatic cancer cells but not with normal pancreatic ductal cells. This combination also induces apoptosis and increases Bax/Bcl2 ratio. ^[3]Combined therapy of Gemcitabine with IFN-γ in Gemcitabine-resistant pancreatic cancer-bearing nude mice shows synergistic therapeutic effects on Gemcitabine-resistant pancreatic cancer bearers. ^[4] The addition of Triciribine can sensitize Gemcitabine treatment, especially in shFKBP5 pancreatic cancer xenograft mice. Combination treatment with Gemcitabine and Triciribine has a better effect on tumor inhibition than either drug alone and that the inhibition effect is more significant in shFKBP5 xenograft mice than wt mice. ^[5] Combination of Guggulsterone (a plant steroid) to Gemcitabine enhances antitumor efficacy. ^[6] Gemcitabine with adjuvant chemotherapy is currently being investigated in a Phase III clinical trial for the treatment of resected pancreatic adenocarcinoma.

Cell Lines

BxPC-3, MIA PaCa-2, and PANC-1 cells

Concentrations

0.2 μM

Incubation Time

24 hours or 48 hours

Methods

BxPC-3, MIA PaCa-2, and PANC-1 cells are seeded in a 96-well plate. After 24 hours, cells are treated with vehicle, DMAPT and/or Gemcitabine for an additional 24 hours or 48 hours. Apoptosis is quantified using the Cell Death Detection ELISA to detect the amount of cytoplasmic histone-associated DNA fragments and expressed relative to vehicle-treated cells.

Animal Models

Athymic nude mice with MIA PaCa-2 cells

Formulation

Phosphate-buffered saline

Doses

50 mg/kg or 100 mg/kg

Administration

Administered via i.p.