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Research Area
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Description
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Cancer |
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Biological Activity
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Description
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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. |
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Targets
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PANC1 |
MIAPaCa2 |
BxPC3 |
Capan2 cell lines |
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IC50 |
50 nM |
40 nM |
18 nM |
12 nM [1] |
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In Vitro
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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] |
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In Vivo
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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] |
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Clinical Trials
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Gemcitabine plus PEGPH20 has entered in a phase II clinical trial in the treatmentof the stage IV pancreatic cancer. |
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Features
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Gemcitabine has been used for pancreatic cancer as the most effective anticancer drug. |
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Combination Therapy
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Description
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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. |
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Protocol
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Cell Assay
[2]
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| 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. |
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Animal Study
[2]
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| 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. |
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References |
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[1] Shi X, et al. Oncology. 2002, 62(4), 354-362.
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[2] Holcomb BK, et al. J Gastrointest Surg. 2012.
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[3] Subramaniam D, et al. Mol Cancer Ther. 2012.
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[4] Kuramitsu Y, et al. Anticancer Res. 2012, 32(6), 2295-2299.
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[5] Hou J, et al. PLoS One. 2012, 7(5), e36252.
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[6] Ahn DW, et al. Pancreas. 2012.
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