乳铁蛋白的抗肿瘤作用机制

doi:10.3760/cma.j.issn.1673-422X.2019.05.007

国际肿瘤学杂志 ›› 2019, Vol. 46 ›› Issue (5): 285-288.doi: 10.3760/cma.j.issn.1673-422X.2019.05.007

乳铁蛋白的抗肿瘤作用机制

莫晓媚，秦鹏飞，赵娜，闫美兴，徐鲁杰

青岛市妇女儿童医院药学部266000

收稿日期:2019-03-05 出版日期:2019-05-08 发布日期:2019-06-14
通讯作者: 徐鲁杰 E-mail:xlujzr@126.com
基金资助:
山东省中医药科技发展计划（2015-382）；青岛市医疗卫生优秀青年医学人才培养项目（2017-9）

Anti-tumor mechanism of lactoferrin

Mo Xiaomei, Qin Pengfei, Zhao Na, Yan Meixing, Xu Lujie

Department of Pharmacy, Qingdao Women and Children′s Hospital, Qingdao 266000, China

Received:2019-03-05 Online:2019-05-08 Published:2019-06-14
Contact: Xu Lujie E-mail:xlujzr@126.com
Supported by:
Traditional Chinese Medicine Science and Technology Development Program of Shandong Province of China (2015-382); Medical and Health Outstanding Young Medical Talent Training Project of Qingdao City of China (2017-9)

摘要/Abstract

摘要： 乳铁蛋白基因的改变与肿瘤发病率的增加有关，然而乳铁蛋白抗肿瘤作用的具体机制尚不清楚。研究发现，在不同的肿瘤细胞中，乳铁蛋白可通过破坏细胞膜、诱导细胞凋亡、阻滞细胞周期、调节细胞免疫反应以及抑制肿瘤血管生成等不同的机制影响肿瘤的发生、发展，进一步了解其机制可为临床预防和治疗肿瘤提供新的思路。

关键词: 乳铁蛋白, 肿瘤, 细胞凋亡

Abstract: Alterations of the lactoferrin gene are associated with an increased incidence of tumor, however, the exact mechanisms involved in the antitumor activity of lactoferrin are still unclear. Several studies suggest that lactoferrin can affect the initiation and development of tumors via different mechanisms such as damaging cell membranes, inducing apoptosis, blocking cell cycle, regulating cellular immune response and inhibiting angiogenesis in different cancer cell lines. Further study about the mechanism can provide new ideas for clinical prevention and treatment of tumors.

Key words: Lactoferrin, Neoplasms, Apoptosis

莫晓媚，秦鹏飞，赵娜，闫美兴，徐鲁杰. 乳铁蛋白的抗肿瘤作用机制[J]. 国际肿瘤学杂志, 2019, 46(5): 285-288.

Mo Xiaomei, Qin Pengfei, Zhao Na, Yan Meixing, Xu Lujie. Anti-tumor mechanism of lactoferrin[J]. Journal of International Oncology, 2019, 46(5): 285-288.

参考文献

［1］ Hao L, Shan Q, Wei J, et al. Lactoferrin: major physiological functions and applications［J］. Curr Protein Pept Sci, 2019, 20(2): 139-144. DOI: 10.2174/1389203719666180514150921. ［2］ Zhang Y, Lima CF, Rodrigues LR. Anticancer effects of lactoferrin: underlying mechanisms and future trends in cancer therapy［J］. Nutr Rev, 2014, 72(12): 763-773. DOI: 10.1111/nure.12155. ［3］ Zhang J, Ling T, Wu H, et al. Reexpression of lactotransferrin, a candidate tumor suppressor inactivated by promoter hypermethylation, impairs the malignance of oral squamous cell carcinoma cells［J］. J Oral Pathol Med, 2015, 44(8): 578-584. DOI: 10.1111/jop.12279. ［4］ Zadvornyi TV, Lukianova NY, Borikun TV, et al. Effects of exogenous lactoferrin on phenotypic profile and invasiveness of human prostate cancer cells (DU145 and LNCaP) in vitro［J］. Exp Oncol, 2018, 40(3): 184-189. ［5］ Furmanski P, Li ZP, Fortuna MB, et al. Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack ironbinding capacity［J］. J Exp Med, 1989, 170(2): 415-429. DOI: 10.1084/jem.170.2.415. ［6］ Kanwar JR, Mahidhara G, Sasidharan S, et al. FebLf nanoformulation targets survivin to kill colon cancer stem cells and maintains absorption of iron, calcium and zinc［J］. Nanomedicine(Lond), 2015, 10(1): 35-55. DOI: 10.2217/nnm.14.132. ［7］ Sanchez CJ, Le Treut T, Boehrer A, et al. Natural killer cells and malignant haemopathies: a model for the interaction of cancer with innate immunity［J］. Cancer Immunol Immunother, 2011, 60(1): 1-13. DOI: 10.1007/s00262-010-0898-x. ［8］ Riedl S, Rinner B, Schaider H, et al. Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine［J］. Biometals, 2014, 27(5): 981-997. DOI: 10.1007/s10534-014-9749-0. ［9］ Riedl S, Leber R, Rinner B, et al. Human lactoferricin derived dipeptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine［J］. Biochimica Biophysica Acta, 2015, 1848(11 Pt A): 2918-2931. DOI: 10.1016/j.bbamem.2015.07.018. ［10］ Camilio KA, Berge G, Ravuri CS, et al. Complete regression and systemic protective immune responses obtained in b16 melanomas after treatment with LTX-315［J］. Cancer Immunol Immunother, 2014, 63(6): 601-613.DOI: 10.1007/s00262-014-1540-0. ［11］ Sheng M, Zhao Y, Zhang A, et al. The effect of LfcinB9 on human ovarian cancer cell SKOV-3 is mediated by inducing apoptosis［J］. J Pept Sci, 2014, 20(10): 803-810. DOI: 10.1002/psc.2670. ［12］ Gibbons JA, Kanwar JR, Kanwar RK. Ironfree and ironsaturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer［J］. BMC Cancer, 2015, 15: 425. DOI: 10.1186/s12885-015-1441-4. ［13］ Wang S, Tu J, Zhou C, et al. The effect of Lfcin-B on non-small cell lung cancer H460 cells is mediated by inhibiting VEGF expression and inducing apoptosis［J］. Arch Pharm Res, 2015, 38(2): 261-271. DOI: 10.1007/s12272-014-0373-x. ［14］ Deng M, Zhang W, Tang H, et al. Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms［J］. Oncogene, 2013, 32(36): 4273-4283. DOI: 10.1038/onc.2012.434. ［15］ Luzi C, Brisdelli F, Iorio R, et al. Apoptotic effects of bovine apolactoferrin on HeLa tumor cells［J］. Cell Biochem Funct, 2017, 35(1): 33-41. DOI: 10.1002/cbf.3242. ［16］ Chea C, Miyauchi M, Inubushi T, et al. Molecular mechanism of inhibitory effects of bovine lactoferrin on the growth of oral squamous cell carcinoma［J］. PLoS One, 2018, 13(1): e0191683. DOI: 10.1371/journal.pone.0191683. ［17］ Jiang R, Lnnerdal B. Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways［J］. Biochem Cell Biol, 2017, 95(1): 99-109. DOI: 10.1139/bcb-2016-0094. ［18］ Zhang Y, Nicolau A, Lima CF, et al. Bovine lactoferrin induces cell cycle arrest and inhibits mTOR signaling in breast cancer cells［J］. Nutr Cancer, 2014, 66 (8): 1371-1385. DOI: 10.1080/01635581.2014.956260. ［19］ Arcella A, Oliva MA, Staffieri S, et al. In vitro and in vivo effect of human lactoferrin on glioblastoma growth［J］. J Neurosurg, 2015, 123(4): 1026-1035. DOI: 10.3171/2014.12. ［20］ Kanwar JR, Palmano KP, Sun X, et al. ‘Ironsaturated’ lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy［J］. Immunol Cell Biol, 2008, 86(3): 277-288. DOI: 10.1038/sj.icb.7100163. ［21］ Li HY, Li M, Luo CC, et al. Lactoferrin exerts antitumor effects by inhibiting angiogenesis in a HT29 human colon tumor model［J］. J Agric Food Chem, 2017, 65(48): 10464-10472. DOI: 10.1021/acs.jafc.7b03390. ［22］ Pereira CS, Guedes JP, Gonalves M, et al. Lactoferrin selectively triggers apoptosis in highly metastatic breast cancer cells through inhibition of plasmalemmal VH⁺ ATPase［J］. Oncotarget, 2016, 7(38): 6214462158. DOI: 10.18632/oncotarget.11394. ［23］ Guedes JP, Pereira CS, Rodrigues LR, et al. Bovine milk lactoferrin selectively kills highly metastatic prostate cancer PC-3 and osteosarcoma MG-63 cells in vitro［J］. Front Oncol, 2018, 8: 200. DOI: 10.3389/fonc.2018.00200. ［24］ Shankaranarayanan JS, Kanwar JR, AI-Juhaishi AJ, et al. Doxorubicin conjugated to immunomodulatory anticancer lactoferrin displays improved cytotoxicity overcoming prostate cancer chemo resistance and inhibits tumour development in TRAMP mice［J］. Sci Rep, 2016, 6: 32062. DOI: 10.1038/srep32062. ［25］ Chekhun VF, Zalutskii IV, Naleskina LA, et al. Modifying effects of lactoferrin in vitro on molecular phenotype of human breast cancer cells［J］. Exp Oncol, 2015, 37(3): 181-186. ［26］ Wang A, Duncan SE, Lesser GJ, et al. Effect of lactoferrin on taste and smell abnormalities induced by chemotherapy: a proteome analysis［J］. Food Funct, 2018, 9(9): 4948-4958. DOI: 10.1039/c8fo00813b. ［27］ Roseanu A, Florian PE, Moisei M, et al. Liposomalization of lactoferrin enhanced its antitumoral effects on melanoma cells［J］. Biometals, 2010, 23(3): 485-492. DOI: 10.1007/s10534-010-9312-6. ［28］ Roy K, Patel YS, Kanwar RK, et al. Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells［J］. Int J Nanomedicine, 2015, 11: 25-44. DOI: 10.2147/IJN.S91810. ［29］ Lin LY, Koh PY, Somani S, et al. Tumor regression following intravenous administration of lactoferrin and lactoferricinbearing dendriplexes［J］. Nanomedicine, 2015, 11(6): 1445-1454. DOI: 10.1016/j.nano.2015.04.006.

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乳铁蛋白的抗肿瘤作用机制

Anti-tumor mechanism of lactoferrin

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