Doxycycline inhibits the adhesion and migration of melanoma cells by inhibiting the expression and phosphorylation of focal adhesion kinase (FAK).
Doxycycline has been found to induce apoptosis and to inhibit the growth of a variety of tumor cells, in addition to its use as an antibiotic. However, the mechanism of its actions, especially at the molecular level, remains unknown and needs to be resolved. A crucial step possibly lies in the early period of doxycycline administration, which leads to a series of cascading effects depicting the consequential biological action of doxycycline on tumor cells. The present study focuses on the early-stage effects of doxycycline administration, specifically at the stages of treatment (before 16h). In this paper, we report that doxycycline inhibits the adhesion and migration of melanoma cells. Afterwards, the cells undergo apoptosis (aniokis). Remarkably, doxycycline also inhibits the expression and phosphorylation of focal adhesion kinase (FAK), a protein tyrosine kinase involved in the regulation of cell adhesion and migration. We further demonstrate that doxycycline down-regulates the activities of MMP-2 and MMP-9, and its effects are stronger than those of an Integrin beta1 antibody. Finally, we suggest that doxycycline might exert its anti-tumor effects by inhibiting FAK signaling pathway. These results provide an insight into the possible mechanisms that underlie the multiple drug actions of doxycycline. The potential use of doxycycline in anti-tumor treatment is promising and warrants further studies.
Sun
Tao
T
Department of Pathology, Tianjin Medical University, Tianjin 300070, PR China.
Zhao
Nan
N
Ni
Chun-sheng
CS
Zhao
Xiu-lan
XL
Zhang
Wen-zhi
WZ
Su
Xin
X
Zhang
Dan-fang
DF
Gu
Qiang
Q
Sun
Bao-cun
BC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline