title: Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase.
abstract: Doxycycline, a tetracycline-based antibiotic, has been reported to attenuate melanoma cell migration through inhibiting the focal adhesion kinase (FAK) signaling pathway. However, it remains to be elucidated whether doxycycline exerts this effect on leukemia cell migration. The present study aimed to examine the role of doxycycline in leukemia cell migration. The invasion capacities of the human leukemia cell lines KG1a (acute myelogenous leukemia) and K562 (chronic myelogenous leukemia) were evaluated using Matrigel® matrix‑coated Transwell® chamber assays; leukemic cell lines treated with doxycycline (1 µg/ml) or anti‑β1‑integrin antibodies were added to the upper chamber, while untreated cells were included as controls. Reverse transcription quantitative polymerase chain reaction was performed in order to further understand the influence of doxycycline treatment on the expression of FAK and gelatinases in the KG1a and K562 leukemic cell lines. In addition, FAK protein expression and phosphorylation were determined using western blot analysis in order to investigate the mechanism by which doxycycline inhibited leukemic cell migration. The results revealed that doxycycline treatment significantly attenuated the migration of KG1a and K562 cells, which was demonstrated to be associated with inhibition of the expression and phosphorylation of FAK. In addition, doxycycline treatment inhibited matrix metalloproteinase (MMP)‑2 and MMP‑9 expression. Furthermore, incubation with blocking anti‑β1‑integrin antibodies had an analogous inhibitory effect on leukemic cell migration to that of doxycycline. In conclusion, the results of the present study suggested that doxycycline attenuated leukemic cell migration through inhibiting the FAK signaling pathway. Therefore, doxycycline may have potential for use as a novel strategy for the treatment of leukemia.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Chunhuai
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, School of Nursing, Anhui Medical University, Hefei, Anhui 230601, P.R. China.
authors.forename: Ru
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Yunxian
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D004318:Doxycycline / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
chemical_list: D000903:Antibiotics, Antineoplastic; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline