Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Iran.
Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Adv Clin Exp Med. 2019 Feb;28(2):151-157. doi: 10.17219/acem/89770.
Aprotinin is a nonspecific serine protease inhibitor, which can inhibit plasminogen-plasmin system and matrix metalloproteinases. Aprotinin has been investigated as an antitumor agent. However, its antineoplastic effects on breast cancer (BC) have not been investigated yet.
The objective of this study was to assess the inhibitory effects of aprotinin on human BC cell lines. We assessed the effects of aprotinin on local invasion and survival of human BC cell lines MDA-MB-231, SK-BR-3 and MCF-7 in vitro.
CHEMICON cell invasion assay kit was used to assess local invasion, and (3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay was used to determine the antiproliferative activity of aprotinin. Human dermal fibroblast (HDF-1) cell line was used as control normal cells.
Cancer cell lines showed more invasion characteristics compared to HDF-1. Aprotinin significantly decreased the invasiveness of MDA-MB-231 in concentrations of 1 trypsin inhibitor unit (TIU)/mL, 1.3 TIU/mL and 1.7 TIU/mL in comparison with the untreated group (analysis of variance (ANOVA) p < 0.001). Treatment of SK-BR-3 with 1.3 TIU/mL aprotinin caused no significant reduction in invasiveness (p = 0.06). Treatment with different concentrations of aprotinin significantly decreased the surviving fraction and inhibited the growth of all cell lines tested in this study (analysis of variance (ANOVA) p < 0.001). Compared to cancer cell lines, normal HDF-1 cell line showed less sensitivity to antiproliferative effects of aprotinin, both in low and high doses.
Aprotinin significantly inhibited the growth of human breast cancer cell lines MDA-MB-231, SK-BR-3 and MCF-7, and normal fibroblast cell line HDF-1. The growth inhibitory effect was more dominant in cancer cell lines. Inhibition of local invasion by aprotinin was significant only in the case of MDA-MB-231. Future molecular studies could shed further lights on mechanisms underlying antineoplastic effects of aprotinin and its potential therapeutic effects.
抑肽酶是一种非特异性丝氨酸蛋白酶抑制剂，可抑制纤溶酶原-纤溶酶系统和基质金属蛋白酶。抑肽酶已被研究作为一种抗肿瘤药物。然而，它在乳腺癌（BC）中的抗肿瘤作用尚未得到研究。
本研究旨在评估抑肽酶对人乳腺癌细胞系的抑制作用。我们评估了抑肽酶对人乳腺癌细胞系 MDA-MB-231、SK-BR-3 和 MCF-7 的体外局部侵袭和生存能力的影响。
采用 CHEMICON 细胞侵袭试剂盒评估局部侵袭，采用（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）四唑还原（MTT）测定法测定抑肽酶的抗增殖活性。人真皮成纤维细胞（HDF-1）细胞系用作对照正常细胞。
与 HDF-1 相比，癌细胞系表现出更多的侵袭特征。与未处理组相比，浓度为 1 胰蛋白酶抑制剂单位（TIU）/mL、1.3 TIU/mL 和 1.7 TIU/mL 的抑肽酶显著降低了 MDA-MB-231 的侵袭性（方差分析（ANOVA）p < 0.001）。用 1.3 TIU/mL 抑肽酶处理 SK-BR-3 不会导致侵袭性显著降低（p = 0.06）。用不同浓度的抑肽酶处理可显著降低所有受试细胞系的存活分数并抑制其生长（方差分析（ANOVA）p < 0.001）。与癌细胞系相比，正常的 HDF-1 细胞系对抑肽酶的抗增殖作用的敏感性较低，无论是低剂量还是高剂量。
抑肽酶显著抑制人乳腺癌细胞系 MDA-MB-231、SK-BR-3 和 MCF-7 以及正常成纤维细胞系 HDF-1 的生长。在癌细胞系中，生长抑制作用更为明显。只有在 MDA-MB-231 中，抑肽酶对局部侵袭的抑制作用才显著。未来的分子研究可以进一步阐明抑肽酶抗肿瘤作用及其潜在治疗效果的机制。
