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Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase

  • Authors:
    • Chunhuai Wang
    • Ru Xiang
    • Xiangzhong Zhang
    • Yunxian Chen
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Internal Medicine, School of Nursing, Anhui Medical University, Hefei, Anhui 230601, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 3374-3380
    |
    Published online on: May 25, 2015
       https://doi.org/10.3892/mmr.2015.3833
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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.
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1 

Chiang AC and Massagué J: Molecular basis of metastasis. New Engl J Med. 359:2814–2823. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Friedl P and Alexander S: Cancer invasion and the microenvironment: Plasticity and reciprocity. Cell. 147:992–1009. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Nagase H and Woessner JF Jr: Matrix metalloproteinases. J Biol Chem. 274:21491–21494. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI

5 

McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG and Frame MC: The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer. 5:505–515. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Rolain JM, Boulos A, Mallet MN and Raoult D: Correlation between ratio of serum doxycycline concentration to MIC and rapid decline of antibody levels during treatment of Q fever endocarditis. Antimicrob Agents Chemother. 49:2673–2676. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Fife RS, Sledge GW Jr, Sissons S and Zerler B: Effects of tetracyclines on angiogenesis in vitro. Cancer Lett. 153:75–78. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Iwasaki H, Inoue H, Mitsuke Y, Badran A, Ikegaya S and Ueda T: Doxycycline induces apoptosis by way of caspase-3 activation with inhibition of matrix metalloproteinase in human T-lymphoblastic leukemia CCRF-CEM cells. J Lab Clin Med. 140:382–386. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Fife RS, Sledge GW Jr, Roth BJ and Proctor C: Effects of doxycycline on human prostate cancer cells in vitro. Cancer Lett. 127:37–41. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Tu G, Xu W, Huang H and Li S: Progress in the development of matrix metalloproteinase inhibitors. Curr Med Chem. 15:1388–1395. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Sun T, Zhao N, Ni CS, et al: Doxycycline inhibits the adhesion and migration of melanoma cells by inhibiting the expression and phosphorylation of focal adhesion kinase (FAK). Cancer Lett. 285:141–150. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Mitra SK, Hanson DA and Schlaepfer DD: Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 6:56–68. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Freireich EJ: Acute leukemia. A prototype of disseminated cancer. Cancer. 53:2026–2033. 1984. View Article : Google Scholar : PubMed/NCBI

14 

Janowska-Wieczorek A, Marquez LA, Matsuzaki A, et al: Expression of matrix metalloproteinases (MMP-2 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in acute myelogenous leukaemia blasts: comparison with normal bone marrow cells. Br J Haematol. 105:402–411. 1999. View Article : Google Scholar : PubMed/NCBI

15 

Recher C, Ysebaert L, Beyne-Rauzy O, et al: Expression of focal adhesion kinase in acute myeloid leukemia is associated with enhanced blast migration, increased cellularity and poor prognosis. Cancer Res. 64:3191–3197. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Berken A, Abel J and Unfried K: beta1-integrin mediates asbestos-induced phosphorylation of AKT and ERK1/2 in a rat pleural mesothelial cell line. Oncogene. 22:8524–8528. 2003.PubMed/NCBI

17 

Ramakers C, Ruijter JM, Deprez RH and Moorman AF: Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett. 339:62–66. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Hanks SK, Ryzhova L, Shin NY and Brabek J: Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front Biosci. 8:d982–996. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Adimora AA: Treatment of uncomplicated genital Chlamydia trachomatis infections in adults. Clin Infect Dis. 35(Suppl 2): S183–S186. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Olson MW, Ruzin A, Feyfant E, Rush TS III, O'Connell J and Bradford PA: Functional, biophysical and structural bases for antibacterial activity of tigecycline. Antimicrob Agents Chemother. 50:2156–2166. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Fife RS and Sledge GW Jr: Effects of doxycycline on in vitro growth, migration and gelatinase activity of breast carcinoma cells. J Lab Clin Med. 125:407–411. 1995.PubMed/NCBI

22 

Pilkington GJ, Parker K and Murray SA: Approaches to mitochondrially mediated cancer therapy. Semin Cancer Biol. 18:226–235. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Kroon AM, Dontje BH, Holtrop M and Van den Bogert C: The mitochondrial genetic system as a target for chemotherapy: tetracyclines as cytostatics. Cancer Lett. 25:33–40. 1984. View Article : Google Scholar : PubMed/NCBI

24 

van den Bogert C, van Kernebeek G, de Leij L and Kroon AM: Inhibition of mitochondrial protein synthesis leads to proliferation arrest in the G1-phase of the cell cycle. Cancer Lett. 32:41–51. 1986. View Article : Google Scholar : PubMed/NCBI

25 

Sun B, Zhang S, Zhang D, et al: Doxycycline influences microcirculation patterns in B16 melanoma. Exp Biol Med (Maywood). 232:1300–1307. 2007. View Article : Google Scholar

26 

Saikali Z and Singh G: Doxycycline and other tetracyclines in the treatment of bone metastasis. Anti-cancer Drugs. 14:773–778. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Gilmore AP, Owens TW, Foster FM and Lindsay J: How adhesion signals reach a mitochondrial conclusion-ECM regulation of apoptosis. Curr Opin Cell Biol. 21:654–661. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Sieg DJ, Hauck CR, Ilic D, et al: FAK integrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol. 2:249–256. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Golubovskaya VM and Cance W: Focal adhesion kinase and p53 signal transduction pathways in cancer. Front Biosci. 15:901–912. 2010. View Article : Google Scholar

30 

Costa P, Scales TM, Ivaska J and Parsons M: Integrin-specific control of focal adhesion kinase and RhoA regulates membrane protrusion and invasion. PLoS One. 8:e746592013. View Article : Google Scholar : PubMed/NCBI

31 

Duivenvoorden WC, Vukmirović-Popović S, Kalina M, Seidlitz E and Singh G: Effect of zoledronic acid on the doxycycline-induced decrease in tumour burden in a bone metastasis model of human breast cancer. Br J Cancer. 96:1526–1531. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Mon NN, Ito S, Senga T and Hamaguchi M: FAK signaling in neoplastic disorders: a linkage between inflammation and cancer. Ann N Y Acad Sci. 1086:199–212. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Dutta A, Sen T and Chatterjee A: Culture of K562 human myeloid leukemia cells in presence of fibronectin expresses and secretes MMP-9 in serum-free culture medium. Int J Clin Exp Pathol. 3:288–302. 2010.PubMed/NCBI

34 

Wang C, Chen Z, Li Z and Cen J: The essential roles of matrix metalloproteinase-2, membrane type 1 metalloproteinase and tissue inhibitor of metalloproteinase-2 in the invasive capacity of acute monocytic leukemia SHI-1 cells. Leuk Res. 34:1083–1090. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Liesveld JL, Winslow JM, Frediani KE, Ryan DH and Abboud CN: Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells. Blood. 81:112–121. 1993.PubMed/NCBI

36 

Guo-Bao W, Xiao-Qin C, Qi-Rong G, Jie L, Gui-Nan L and Yue L: Arsenic Trioxide overcomes cell adhesion-mediated drug resistance through down-regulating the expression of beta (1)-integrin in K562 chronic myelogenous leukemia cell line. Leuk Lymphoma. 51:1090–1097. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Cheng SY, Sun G, Schlaepfer DD and Pallen CJ: Grb2 promotes integrin-induced focal adhesion kinase (FAK) autophos-phorylation and directs the phosphorylation of protein tyrosine phosphatase alpha by the Src-FAK kinase complex. Mol Cell Biol. 34:348–361. 2014. View Article : Google Scholar :

38 

Brunton VG, Avizienyte E, Fincham VJ, et al: Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res. 65:1335–1342. 2005. View Article : Google Scholar : PubMed/NCBI

39 

Katz BZ, Romer L, Miyamoto S, et al: Targeting membrane-localized focal adhesion kinase to focal adhesions: roles of tyrosine phosphorylation and SRC family kinases. J Biol Chem. 278:29115–29120. 2003. View Article : Google Scholar : PubMed/NCBI

40 

Li S, Butler P, Wang Y, et al: The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells. Natl Acad Sci USA. 99:3546–3551. 2002. View Article : Google Scholar

41 

Brinckerhoff CE and Matrisian LM: Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol. 3:207–214. 2002. View Article : Google Scholar : PubMed/NCBI

42 

Lundell BI, McCarthy JB, Kovach NL and Verfaillie CM: Activation-dependent alpha5beta1 integrin-mediated adhesion to fibronectin decreases proliferation of chronic myelogenous leukemia progenitors and K562 cells. Blood. 87:2450–2458. 1996.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang C, Xiang R, Zhang X and Chen Y: Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase. Mol Med Rep 12: 3374-3380, 2015.
APA
Wang, C., Xiang, R., Zhang, X., & Chen, Y. (2015). Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase. Molecular Medicine Reports, 12, 3374-3380. https://doi.org/10.3892/mmr.2015.3833
MLA
Wang, C., Xiang, R., Zhang, X., Chen, Y."Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase". Molecular Medicine Reports 12.3 (2015): 3374-3380.
Chicago
Wang, C., Xiang, R., Zhang, X., Chen, Y."Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase". Molecular Medicine Reports 12, no. 3 (2015): 3374-3380. https://doi.org/10.3892/mmr.2015.3833
Copy and paste a formatted citation
x
Spandidos Publications style
Wang C, Xiang R, Zhang X and Chen Y: Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase. Mol Med Rep 12: 3374-3380, 2015.
APA
Wang, C., Xiang, R., Zhang, X., & Chen, Y. (2015). Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase. Molecular Medicine Reports, 12, 3374-3380. https://doi.org/10.3892/mmr.2015.3833
MLA
Wang, C., Xiang, R., Zhang, X., Chen, Y."Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase". Molecular Medicine Reports 12.3 (2015): 3374-3380.
Chicago
Wang, C., Xiang, R., Zhang, X., Chen, Y."Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase". Molecular Medicine Reports 12, no. 3 (2015): 3374-3380. https://doi.org/10.3892/mmr.2015.3833
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