An anticancer nucleoside analog
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].
吉西他滨是 DNA 合成的抑制剂 [1]。
DNA 合成是脱氧核糖核酸 (DNA) 分子的自然产物，在细胞生长中起着重要作用。
吉西他滨是一种活性化学治疗剂，可破坏 DNA 复制。在肿瘤细胞中，吉西他滨激活检查点激酶 2 (Chk2) 和共济失调-毛细血管扩张突变激酶 (ATM)，后者调节细胞凋亡、DNA 修复和细胞周期停滞。此外，吉西他滨激活 Rad9-Hus1-Rad1 复合物和蛋白激酶 ATM 和 ATR 以及检查点激酶 1 (Chk1)，从而阻断细胞周期进程并影响 DNA 修复 [1]。 Gemcitabine 是一种 DNA 合成抑制剂，具有抗肿瘤活性。在人骨肉瘤细胞系HOS和MG63中，吉西他滨抑制DNA合成并诱导细胞凋亡[2]。
在接种小鼠骨肉瘤细胞系 LM8 的 C3H 小鼠中，吉西他滨诱导细胞凋亡并减小原发肿瘤的大小。此外，它还能抑制肺部的转移性病灶 [2]。在感染 LP-BM5 小鼠白血病病毒的 C57Bl/6 小鼠中，吉西他滨显着抑制疾病进展。此外，吉西他滨还能降低脾脏大小、原病毒水平和血浆 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.
| Cell experiment [1]: | |
|
Cell lines |
HeLa cells, K562 cells, HOS and MG63 cell lines. |
|
Preparation method |
The solubility of this compound in DMSO﹥10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
100 nM gemcitabine for 3 h in HeLa cells for immunofluorescence, 500 nM gemcitabine for 6 h for SDS-PAGE |
|
Applications |
In Hela cells and K562 cells, gemcitabine activated both the ATR/Chk1 and ATM/Chk2 signaling pathways. (ATR: ataxia-telangiectasia mutated and Rad3-related kinase; Chk: checkpoint kinase; ATM: ataxia-telangiectasia mutated kinase). 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. |
| Animal experiment [2]: | |
|
Animal models |
Female C57BL/6 mice infected with LP-BM5 MuLV |
|
Dosage form |
1, 2, 4 mg/kg/day for 8 week by injection. |
|
Application |
Mice treated with 1 or 2 mg/kg/day had an average ratio of spleen to body weight that was significantly lower than the infected with virus, untreated mice. Treatment with gemcitabine decreased MAIDS associated lesions in the lymph nodes. IgM levels from mice treated with 2 mg/kg/day of gemcitabine were significantly lower than that seen in the uninfected animals. Gemcitabine decreased provirus levels. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
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. |
|
动态评分
0.0