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Silk fibroin peptide suppresses proliferation and induces apoptosis and cell cycle arrest in human lung cancer cells.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2018-Jun-19 , DOI: 10.1038/s41401-018-0048-0
Mei-sa Wang , Yi-bo Du , Hui-ming Huang , Zhong-ling Zhu , Shuang-shuang Du , Shao-yong Chen , Hong-ping Zhao , Zhao Yan

Silkworm cocoon was recorded to cure carbuncle in the Compendium of Materia Medica. Previous studies have demonstrated that the supplemental silk protein sericin exhibits anticancer activity. In the present study, we investigated the effects of silk fibroin peptide (SFP) extracted from silkworm cocoons against human lung cancer cells in vitro and in vivo and its possible anticancer mechanisms. SFP that we prepared had high content of glycine (~ 30%) and showed a molecular weight of ~ 10 kDa. Intragastric administration of SFP (30 g/kg/d) for 14 days did not affect the weights, vital signs, routine blood indices, and blood biochemical parameters in mice. MTT assay showed that SFP dose-dependently inhibited the growth of human lung cancer A549 and H460 cells in vitro with IC50 values of 9.921 and 9.083 mg/mL, respectively. SFP also dose-dependently suppressed the clonogenic activity of the two cell lines. In lung cancer H460 xenograft mice, intraperitoneal injection of SFP (200 or 500 mg/kg/d) for 40 days significantly suppressed the tumor growth, but did not induce significant changes in the body weight. We further examined the effects of SFP on cell cycle and apoptosis in H460 cells using flow cytometry, which revealed that SFP-induced cell cycle arrest at the S phase, and then promoted cell apoptosis. We demonstrated that SFP (20-50 mg/mL) dose-dependently downregulates Bcl-2 protein expression and upregulates Bax protein in H460 cells during cell apoptosis. The results suggest that SFP should be studied further as a novel therapeutic agent for the treatment of lung cancer.

中文翻译:

丝素蛋白肽抑制人肺癌细胞的增殖,并诱导其凋亡和细胞周期停滞。

在《本草纲目》中记录了蚕茧可以治愈虫。先前的研究表明,补充的丝蛋白丝胶具有抗癌活性。在本研究中,我们研究了从蚕茧中提取的丝素蛋白肽(SFP)在体外和体内对人肺癌细胞的作用及其可能的抗癌机制。我们制备的SFP的甘氨酸含量高(约30%),分子量约为10 kDa。胃内给予SFP(30 g / kg / d)14天未影响小鼠的体重,生命体征,常规血液指数和小鼠血液生化参数。MTT分析表明,SFP可以在体外用IC 50剂量依赖性地抑制人肺癌A549和H460细胞的生长值分别为9.921和9.083 mg / mL。SFP还剂量依赖性地抑制了两种细胞系的克隆形成活性。在肺癌H460异种移植小鼠中,腹膜内注射SFP(200或500 mg / kg / d)持续40天可显着抑制肿瘤生长,但不会引起体重的显着变化。我们使用流式细胞仪进一步检查了SFP对H460细胞的细胞周期和凋亡的影响,结果表明SFP诱导的细胞周期停滞在S期,然后促进了细胞凋亡。我们证明了SFP(20-50 mg / mL)在细胞凋亡过程中剂量依赖性地下调H460细胞中的Bcl-2蛋白表达并上调Bax蛋白。结果表明,SFP应该作为一种新型的肺癌治疗药物进行进一步的研究。
更新日期:2018-06-19
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