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Published on: June 13, 2018
Fluoxetine Inhibits STAT3-mediated Survival and Invasion of Osteosarcoma Cells
Wei-Ting Chen1, Yuan-Hsin Tsai2,3, Peggy Tan4
1Department of Psychosomatics, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C.
Background/Aim:
Osteosarcoma (OS) is a common primary malignancy of bone in adolescents. Its highly metastatic characteristics can lead to treatment failure and poor prognosis. Although standard treatments, including surgery, radiotherapy, and chemotherapy, have progressed in the past decade, treatment options to overcome metastatic progression remain sparse. Fluoxetine, an anti-depressant, has been widely used in patients with cancer for their mental issues and was reported to possess antitumor potential. However, the effect of fluoxetine on OS remains unclear.
Materials And Methods:
In this study, we used cell viability, invasion/migration transwell, wound-healing and aortic ring assays to identify the effects of fluoxetine on metastasis and progression in OS.
Results:
Fluoxetine induced cytotoxicity in OS cells by activating both extrinsic/intrinsic apoptosis signaling pathways. Proliferation and anti-apoptosis-related factors such as cyclin D1 and X-linked inhibitor of apoptosis were suppressed by fluoxetine. Additionally, fluoxetine suppressed the invasive/migratory abilities of OS and inhibited the development of angiogenesis by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Metastasis-associated factors, vascular endothelial growth factors, matrix metallopeptidase 2 and -9, were all reduced in OS cells by fluoxetine treatment.
Conclusion:
Fluoxetine not only induces cytotoxicity and apoptosis of OS cells, but also suppresses metastasis and angiogenesis by targeting STAT3.
Insights
Fluoxetine demonstrates significant antitumor potential against osteosarcoma (OS) by inducing cancer cell death and inhibiting metastasis. This antidepressant effectively suppresses tumor growth and spread by targeting key signaling pathways involved in progression.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Osteosarcoma (OS) is a prevalent bone cancer in adolescents with high metastatic potential, leading to poor prognosis.
- Current treatments for OS have limitations in overcoming metastatic progression.
- Fluoxetine, an antidepressant, has shown potential antitumor effects, but its impact on OS is not well understood.
Purpose of the Study:
- To investigate the effects of fluoxetine on osteosarcoma cell metastasis and progression.
- To elucidate the mechanisms by which fluoxetine influences OS cell behavior.
Main Methods:
- Cell viability assays were employed to assess cytotoxicity.
- Transwell invasion and migration assays, along with wound-healing assays, were used to evaluate metastatic potential.
- Aortic ring assays were performed to study angiogenesis inhibition.
- Western blotting or similar techniques were likely used to analyze protein expression and phosphorylation, particularly for STAT3.
Main Results:
- Fluoxetine induced significant cytotoxicity in OS cells via apoptosis.
- The drug suppressed proliferation and anti-apoptotic factors like cyclin D1 and X-linked inhibitor of apoptosis.
- Fluoxetine inhibited OS cell invasion, migration, and angiogenesis by reducing STAT3 phosphorylation.
- Key metastasis-associated factors, including VEGF, MMP-2, and MMP-9, were downregulated by fluoxetine.
Conclusions:
- Fluoxetine exhibits potent anti-osteosarcoma activity, inducing cytotoxicity and apoptosis.
- The drug effectively suppresses OS metastasis and angiogenesis.
- Targeting STAT3 is a key mechanism through which fluoxetine exerts its anti-cancer effects in osteosarcoma.
