Background:

Gemcitabine is an inhibitor of DNA synthesis [1].

DNA synthesis is a natural creation of deoxyribonucleic acid (DNA) molecules and plays an important role in cell growth.

Gemcitabine is an active chemotherapeutic agents that disrupt DNA replication. In tumor cells, gemcitabine activated checkpoint kinase 2 (Chk2) and ataxia-telangiectasia mutated kinase (ATM), which regulated apoptosis, DNA repair and cell-cycle arrest. Also, gemcitabine activated the Rad9-Hus1-Rad1 complex and the protein kinases ATM and ATR and checkpoint kinase 1 (Chk1), which blocked cell-cycle progression and influence DNA repair [1]. Gemcitabine is a DNA synthesis inhibitor with anti-tumor activity. In human osteosarcoma cell lines HOS and MG63, gemcitabine inhibited DNA synthesis and induced apoptosis [2].

In C3H mice inoculated with murine osteosarcoma cell line LM8, gemcitabine induced cell apoptotics and reduced the size of primary tumor. Also, it inhibited metastatic lesions in the lung [2]. In C57Bl/6 mice infected with LP-BM5 murine leukemia virus, gemcitabine significantly inhibited disease progression. Also, gemcitabine reduced spleen size, provirus levels and plasma IgM [3].

参考文献:
[1].  Karnitz LM, Flatten KS, Wagner JM, et al. Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival. Mol Pharmacol, 2005, 68(6): 1636-1644.
[2].  Ando T, Ichikawa J, Okamoto A, et al. Gemcitabine inhibits viability, growth, and metastasis of osteosarcoma cell lines. J Orthop Res, 2005, 23(4): 964-969.
[3].  Clouser CL, Holtz CM, Mullett M, et al. Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine. PLoS One, 2011, 6(1): e15840.