Gemcitabine HCl is a chemically synthesized deoxycytidine derivative and a DNA synthesis inhibitor that can inhibit human serum Paraoxonase 1（PON1） activity in vitro with an IC50 value of 26.610mM. In addition, Gemcitabine HCl can also be used to treat cancers such as breast cancer, bladder cancer and pancreatic cancer [1-3].
Gemcitabine HCl can inhibit a variety of cell activities, with IC50 values of 240.4±29.0μM (CCRF-CEM/dCK−/− cells), 14.7±2.8nM (TC-1 cells), and 36.7 ± 5.1μM (TC-1-GR cells), 49.7 ± 17.7nM (MIA PaCa-2 cells), 2.12 ± 0.11 (MCF-7 cells) and 2.40 ± 0.15μM (MDA-MB-231 cells)[2-3]. In pancreatic cancer cell lines COLO 357 and L3.6pl, Gemcitabine HCl can significantly inhibit cell growth and increase apoptosis[4].
In a pancreatic cancer patient-derived xenograft mouse model, LPAR4 expression was significantly increased in tumors of mice treated with Gemcitabine HCl (100mg/kg) [5]. In SCID mice orthotopically implanted with COLO 357 cells, Gemcitabine HCl (80mg/kg) inhibited tumor growth in mice and reduced tumor weight by 27%[4]. Gemcitabine HCl (5mg/kg) can inhibit tumor growth in xenotransplantation models in nude mice, and down-regulation of hsa-miR-3178 increases the sensitivity of tumor cells to Gemcitabine HCl[6].
References:
[1] Türkeş C, Söyüt H, Beydemir Ş. Inhibition effects of gemcitabine hydrochloride, acyclovir, and 5-fluorouracil on human serum paraoxonase-1 (hPON1): in vitro[J]. Open J Biochem, 2013, 1: 10-15.
[2] Yalcin T E, Ilbasmis-Tamer S, Takka S. Antitumor activity of gemcitabine hydrochloride loaded lipid polymer hybrid nanoparticles (LPHNs): In vitro and in vivo[J]. International journal of pharmaceutics, 2020, 580: 119246.
[3] Lansakara, P.D., B.L. Rodriguez, and Z. Cui, Synthesis and in vitro evaluation of novel lipophilic monophosphorylated gemcitabine derivatives and their nanoparticles. Int J Pharm, 2012. 429(1-2): p. 123-34.
[4] Banerjee, S., et al., Molecular evidence for increased antitumor activity of gemcitabine by genistein in vitro and in vivo using an orthotopic model of pancreatic cancer. Cancer Res, 2005. 65(19): p. 9064-72.
[5] Wu C, Rakhshandehroo T, Wettersten HI, Campos A, von Schalscha T, Jain S, Yu Z, Tan J, Mose E, Childers BG, Lowy AM, Weis SM, Cheresh DA. Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation. Nat Cell Biol. 2023 Feb;25(2):309-322.
[6] Gu J, Huang W, Wang X, Zhang J, Tao T, Zheng Y, Liu S, Yang J, Chen ZS, Cai CY, Li J, Wang H, Fan Y. Hsa-miR-3178/RhoB/PI3K/Akt, a novel signaling pathway regulates ABC transporters to reverse gemcitabine resistance in pancreatic cancer. Mol Cancer. 2022 May 10;21(1):112.
Gemcitabine HCl是化学合成的脱氧胞苷衍生物，是一种DNA合成抑制剂，可在体外抑制人血清对氧磷酶1（PON1）活性，IC50值为26.610mM。此外，Gemcitabine HCl还可用于癌症的治疗，如乳腺癌、膀胱癌和胰腺癌等[1-3]。
Gemcitabine HCl可抑制多种细胞活性，IC50值为240.4±29.0μM（CCRF-CEM/dCK−/−细胞）、14.7±2.8nM（TC-1细胞）、36.7 ± 5.1μM（TC-1-GR细胞）、49.7 ± 17.7nM（MIA PaCa-2细胞）、2.12±0.11（MCF-7细胞）和2.40±0.15μM（MDA-MB-231细胞）[2-3]。在胰腺癌细胞系COLO 357和L3.6pl中，Gemcitabine HCl可以显著抑制细胞生长并促进细胞凋亡[4]。
在胰腺癌患者来源的异种移植小鼠模型中，Gemcitabine HCl（100mg/kg）处理的小鼠肿瘤中LPAR4表达显着升高[5]。在原位植入COLO 357细胞的SCID小鼠中，Gemcitabine HCl（80mg/kg）可抑制小鼠肿瘤生长，可使肿瘤重量减少27%[4]。Gemcitabine HCl（5mg/kg）可抑制裸鼠异种移植模型中肿瘤的生长，并且hsa-miR-3178下调增加了体内肿瘤细胞对Gemcitabine HCl的敏感性[6]。