Title |
Minocycline Suppresses Interleukine-6, Its Receptor System and Signaling Pathways and Impairs Migration, Invasion and Adhesion Capacity of Ovarian Cancer Cells: In Vitro and In Vivo Studies
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Published in |
PLOS ONE, April 2013
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DOI | 10.1371/journal.pone.0060817 |
Pubmed ID | |
Authors |
Parvin Ataie-Kachoie, David L. Morris, Mohammad H. Pourgholami |
Abstract |
Interleukin (IL)-6 has been shown to be a major contributing factor in growth and progression of ovarian cancer. The cytokine exerts pro-tumorigenic activity through activation of several signaling pathways in particular signal transducer and activator of transcription (STAT3) and extracellular signal-regulated kinase (ERK)1/2. Hence, targeting IL-6 is becoming increasingly attractive as a treatment option in ovarian cancer. Here, we investigated the effects of minocycline on IL-6 and its signaling pathways in ovarian cancer. In vitro, minocycline was found to significantly suppress both constitutive and IL-1β or 4-hydroxyestradiol (4-OH-E2)-stimulated IL-6 expression in human ovarian cancer cells; OVCAR-3, SKOV-3 and CAOV-3. Moreover, minocycline down-regulated two major components of IL-6 receptor system (IL-6Rα and gp130) and blocked the activation of STAT3 and ERK1/2 pathways leading to suppression of the downstream product MCL-1. In female nude mice bearing intraperitoneal OVCAR-3 tumors, acute administration (4 and 24 h) of minocycline (30 mg/kg) led to suppression of IL-6. Even single dose of minocycline was effective at significantly lowering plasma and tumor IL-6 levels. In line with this, tumoral expression of p-STAT3, p-ERK1/2 and MCL-1 were decreased in minocycline-treated mice. Evaluation of the functional implication of minocycline on metastatic activity revealed the capacity of minocycline to inhibit cellular migration, invasion and adhesion associated with down-regulation of matrix metalloproteinases (MMP)-2 and 9. Thus, the data suggest a potential role for minocycline in suppressing IL-6 expression and activity. These effects may prove to be an important attribute to the upcoming clinical trials of minocycline in ovarian cancer. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 32 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 8 | 25% |
Student > Doctoral Student | 6 | 19% |
Researcher | 6 | 19% |
Student > Postgraduate | 2 | 6% |
Student > Master | 2 | 6% |
Other | 3 | 9% |
Unknown | 5 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 11 | 34% |
Agricultural and Biological Sciences | 7 | 22% |
Nursing and Health Professions | 2 | 6% |
Biochemistry, Genetics and Molecular Biology | 1 | 3% |
Social Sciences | 1 | 3% |
Other | 3 | 9% |
Unknown | 7 | 22% |