01 September 2018 : Laboratory Research
[Retracted: 25 Mar 2021] Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway
Fengli Zhang12BCDEF, Huixiao Chen2BCDEF, Jing Du2BCF, Bin Wang2BD, Lixiao Yang2ACDEFG*DOI: 10.12659/MSM.909745
Med Sci Monit 2018; 24: LBR6093-6101
Abstract
BACKGROUND: Ovarian cancer is considered one of the lethal cancers responsible for high mortality and morbidity across the world. The prognosis and the survival rate of ovarian cancer is far from decent. Cysteine-rich 61 (Cyr61) also known as CCN1, is a member of CCN-family of growth factors, reported to be significantly overexpressed in several malignancies which include, but are not limited to, ovarian cancer. Recent studies have revealed that women with type 2 diabetes mellitus have an elevated risk of ovarian cancer. Hence, administration of an antidiabetic drug with anticancer effects such as metformin may act as an effective therapeutic regime against ovarian cancer.
MATERIAL AND METHODS: Cell viability and apoptosis were examined by MTT and Annexin V/PI double staining respectively. Cell migration was determined by Boyden Chamber assay. Transient knockdown of Cyr61 in ovarian cancer cells was achieved by transecting the cells with siRNA for Cyr61using Lipofectamine 2000.
RESULTS: Our results indicated that treatment of ovarian cancer cells with metformin caused significant downregulation of Cyr61 protein expression levels ultimately favoring apoptosis. Transient knockdown of Cyr61 resulted in the inhibition of cell proliferation and migration. This was also associated with the concomitant downregulation of pAkt and pmTOR confirming the role of Cyr61 as an upstream modulator of Akt signaling. Conversely the extracellular supplementation of recombinant Cyr61 attenuates the cytotoxic properties of metformin in ovarian cancer cells.
CONCLUSIONS: Taken together, we concluded that metformin exhibits anticancer effects and Cyr61 acts as a direct target for metformin in ovarian cancer cells.
Keywords: Retracted Publication
Retraction note
- Download PDF
- Order reprints
- Export Article
- Related articles
- Share by email
- Metrics
857 2
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
05 Mar 2024 : Clinical Research
Role of Critical Shoulder Angle in Degenerative Type Rotator Cuff Tears: A Turkish Cohort StudyMed Sci Monit In Press; DOI: 10.12659/MSM.943703
06 Mar 2024 : Clinical Research
Comparison of Outcomes between Single-Level and Double-Level Corpectomy in Thoracolumbar Reconstruction: A ...Med Sci Monit In Press; DOI: 10.12659/MSM.943797
21 Mar 2024 : Meta-Analysis
Economic Evaluation of COVID-19 Screening Tests and Surveillance Strategies in Low-Income, Middle-Income, a...Med Sci Monit In Press; DOI: 10.12659/MSM.943863
10 Apr 2024 : Clinical Research
Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Dep...Med Sci Monit In Press; DOI: 10.12659/MSM.942612
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952