A Novel Human Recombinant Lactoferrin Inhibits Lung Adenocarcinoma Cell Growth and Migration with No Cytotoxic Effect on Normal Human Epithelial Cells

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2021-11-08 DOI:10.1007/s00005-021-00637-2
Paulina Olszewska, Barbara Pazdrak, Marian L. Kruzel
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引用次数: 9

Abstract

Lung cancer remains the leading cause of cancer death worldwide. Despite the recent advances in cancer treatment, only a subset of patients responds to targeted and immune therapies, and many patients developing resistance after an initial response. Lactoferrin (Lf) is a natural glycoprotein with immunomodulatory and anticancer activities. We produced a novel recombinant human Lf (rhLf) that exhibits glycosylation profile compatible with the natural hLf for potential parenteral therapeutic applications. The aim of this study was to evaluate the anticancer effects of this novel rhLf in human lung adenocarcinoma cells and its mechanisms of action. The results showed a concentration-dependent inhibition of A549 cancer cell growth in response to rhLf. Treatment with 1 mg/ml of rhLf for 24 h and 72 h resulted in a significant inhibition of cancer cell growth by 32% and 25%, respectively. Moreover, rhLf increased fourfold the percentage of early and late apoptotic cells compared to the control. This effect was accompanied by increased levels of caspase-3 activity and cell cycle arrest at the S phase in rhLf-treated cancer cells. Furthermore, rhLf significantly attenuated A549 cell migration. Importantly, treatment of normal human bronchial epithelial (NHBE) cells with rhLf showed the cell viability and morphology comparable to the control. In contrast, chemotherapeutic etoposide induced cytotoxicity in NHBE cells and reduced the cell viability by 40%. These results demonstrate the selective anticancer effects of rhLf against lung adenocarcinoma cells without cytotoxicity on normal human cells. This study highlights a potential for clinical utility of this novel rhLf in patients with lung cancer.

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一种新的重组人乳铁蛋白抑制肺腺癌细胞的生长和迁移,对正常人上皮细胞无细胞毒性作用
癌症仍然是全球癌症死亡的主要原因。尽管癌症治疗最近取得了进展,但只有一小部分患者对靶向和免疫疗法有反应,许多患者在最初反应后出现耐药性。乳铁蛋白是一种具有免疫调节和抗癌活性的天然糖蛋白。我们生产了一种新的重组人Lf(rhLf),其表现出与天然hLf兼容的糖基化特性,用于潜在的胃肠外治疗应用。本研究的目的是评估这种新型rhLf在人肺腺癌细胞中的抗癌作用及其作用机制。结果表明,rhLf对A549癌症细胞生长具有浓度依赖性抑制作用。用1mg/ml的rhLf处理24小时和72小时分别导致癌症细胞生长的显著抑制32%和25%。此外,与对照组相比,rhLf使早期和晚期凋亡细胞的百分比增加了四倍。在rhLf处理的癌症细胞中,这种效应伴随着胱天蛋白酶-3活性水平的增加和S期细胞周期阻滞。此外,rhLf显著减弱A549细胞的迁移。重要的是,用rhLf处理正常人支气管上皮(NHBE)细胞显示出与对照相当的细胞活力和形态。相反,化疗依托泊苷诱导了NHBE细胞的细胞毒性,并使细胞活力降低了40%。这些结果证明了rhLf对肺腺癌细胞的选择性抗癌作用,而对正常人细胞没有细胞毒性。这项研究强调了这种新型rhLf在癌症患者中的临床应用潜力。
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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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