title: Levofloxacin increases the effect of serum deprivation on anoikis of rat nucleus pulposus cells via Bax/Bcl-2/caspase-3 pathway.
abstract: Levofloxacin, a fluoroquinolone, is a widely-used and effective antibiotic. However, various adverse side effects are associated with levofloxacin. The purpose of this study was to further explore the effects of levofloxacin on rat nucleus pulposus cells (NPCs). Inverted phase-contrast microscopy, flow cytometry and caspase-3 activity assays were used and revealed that serum deprivation induced apoptosis, which was markedly increased by levofloxacin in a dose-dependent manner. Simultaneously, levofloxacin decreased cell binding to type II collagen (COL2). Thus, levofloxacin-induced apoptosis exhibits characteristics of anoikis, the process by which cell death is triggered by separation from the extracellular matrix, which contains COL2. Furthermore, real-time quantitative RT-PCR was used to further confirm that levofloxacin downregulates COL2 expression in a dose-dependent manner. At last, western blot was used to find that levofloxacin increased the ratio of Bax/Bcl-2 and active caspase-3 in a dose-dependent manner. Levofloxacin therefore increases the effects of serum deprivation on anoikis by downregulating COL2 in rat NPCs in vitro via Bax/Bcl-2/caspase-3 pathway. This research provides a novel insight into the mechanisms of levofloxacin-induced toxicity and may potentially lead to a better understanding of the clinical effects of levofloxacin, especially in terms of intervertebral disc degeneration.
authors.affiliation: Department of Spinal Surgery and.
authors.forename: Si-Dong
authors.initials: SD
authors.lastname: Yang
authors.forename: Zhi-Long
authors.initials: ZL
authors.lastname: Bai
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Da-Long
authors.initials: DL
authors.lastname: Yang
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Ding
mesh_terms: D000818:Animals; D023102:Anoikis / Q000187:drug effects*; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D004789:Enzyme Activation; D064704:Levofloxacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; D017931:DNA Primers; D051028:bcl-2-Associated X Protein; D064704:Levofloxacin; D053148:Caspase 3
keywords: Apoptosis; collagen; degeneration; intervertebral disc