Bleomycin A5 (hydrochloride) is a glycopeptide antibiotic that acts as the antitumor agent [1]. Bleomycin A5 acts on S stage of cell cycle to snip DNA chain during cell mitosis and disturb the cell proliferation[2]. Bleomycin A5 has been widely used to establish rat models of pulmonary fibrosis and to increase the serum levels of inflammatory cytokines[3].
In vitro, Bleomycin A5 treatment for 72 hours significantly inhibited the viability of nasal polyp-derived fibroblasts (NPDFs), with an IC50 value of 132μM[4]. Treatment with 15μg/ml Bleomycin A5 for 24 hours can increase the levels of caspase-3 and p53, inhibit telomerase activity, and induce apoptosis in ECV304 cells[5]. Treatment with 80μg/ml Bleomycin A5 for 24 hours can induce the expression of p21 in A549 cells, inhibit the expression and phosphorylation of EGFR, and cause cell cycle arrest[6].
In vivo, intratracheal administration of a single dose of Bleomycin A5 (5mg/kg) significantly induced lung inflammation and fibrosis in rats over a period of seven days[7].
References:
[1] Dorr R T, Meyers R, Snead K, et al. Analytical and biological inequivalence of two commercial formulations of the antitumor agent bleomycin[J]. Cancer chemotherapy and pharmacology, 1998, 42(2): 149-154.
[2] Luo Q, Zhao F. The effects of Bleomycin A5 on infantile maxillofacial haemangioma[J]. Head & face medicine, 2011, 7(1): 11.
[3] Wang A, Wang F, Yin Y, et al. Dexamethasone reduces serum level of IL-17 in Bleomycin-A5-induced rats model of pulmonary fibrosis[J]. Artificial Cells, Nanomedicine, and Biotechnology, 2018, 46(4): 783-787.
[4] Wu F, Tian P, Ma Y, et al. Induction of apoptosis in nasal polyp-derived fibroblasts by bleomycin A5 in vitro[J]. Molecular Medicine Reports, 2018, 17(4): 5384-5389.
[5] Huang Y D, Li P, Tong X, et al. Effects of bleomycin A5 on caspase-3, P53, bcl-2 expression and telomerase activity in vascular endothelial cells[J]. Indian Journal of Pharmacology, 2015, 47(1): 55-58.
[6] He Y, Lan Y, Liu Y, et al. Pingyangmycin and bleomycin share the same cytotoxicity pathway[J]. Molecules, 2016, 21(7): 862.
[7] Pan J B, Hou Y H, Zhang G J. Rolipram attenuates bleomycin A5‐induced pulmonary fibrosis in rats[J]. Respirology, 2009, 14(7): 975-982.
Bleomycin A5 (hydrochloride)是一种糖肽类抗生素，具有抗肿瘤活性[1]。Bleomycin A5作用于细胞周期的S期，在细胞有丝分裂过程中切割DNA链，干扰细胞增殖[2]。Bleomycin A5已被广泛用于建立大鼠肺纤维化模型，并用于增加血清中炎症细胞因子的水平[3]。
在体外，Bleomycin A5处理72小时显著抑制了鼻息肉来源成纤维细胞(NPDFs)的活力，IC50值为132μM[4]。使用15μg/ml的Bleomycin A5处理ECV304细胞24小时，可增加caspase-3和p53的水平，抑制端粒酶活性，并诱导细胞凋亡[5]。使用80μg/ml的Bleomycin A5处理A549细胞24小时，可诱导p21的表达，抑制EGFR的表达和磷酸化，并引起细胞周期阻滞[6]。
在体内，单次气管内给予5mg/kg的Bleomycin A5，可在七天内显著诱导大鼠肺部炎症和纤维化[7]。