Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Metformin Synergistically Increases the Anticancer Effects of Lapatinib Through Induction of Apoptosis and Modulation of Akt/Ampk Pathway in Sk-Br3 Breast Cancer Cell Line Publisher



Neamati D1 ; Khedri A1 ; Aberomand M2 ; Hemmati AA3 ; Mohammadzadeh M4 ; Baghbani KA5 ; Mohammadzadeh G6
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  2. 2. Toxicology Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  3. 3. Medicinal Plant Research Center, Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  4. 4. Translational Ophthalmology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Infection Immunity and Inflammation, University of Leicester, Leicester, LE1 7RH, United Kingdom
  6. 6. Hyperlipidemia Research Center, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Source: Iranian Journal of Basic Medical Sciences Published:2021


Abstract

Objective(s): Combination chemotherapy is a beneficial intervention for breast cancer, versus single therapy. We investigated the effect of Metformin (Met) on Lapatinib (Lap)-induced apoptosis in SK-BR3 cells. Materials and Methods: Toxic effect of Met and Lap on SK-BR3 cells was measured using MTT assay. Flow cytometry was used to measure the co-treatment effect of Met on lapatinib-induced apoptosis. The relative expression of Bax, Bcl2, and P21 was measured using a real-time PCR. The activity of caspase 3 and 9 was measured using an ELISA kit. The protein level of AMPK and Akt was determined using Western blot analysis. Results: Metformin and lapatinib alone and combined form showed significant time- and dose-dependent toxic effects on SK-BR3 cell viability. The greatest synergistic inhibitory effect on the cell viability [combination index (CI) = 0.51] was remarkable at Met 100 mM combined with Lap 100 nM. The combination has a stronger apoptotic death (46%) versus lapatinib alone. The combination considerably increased the mRNA expression of Bax and P21, and caspase 3 and 9 activity, while, decreasing the mRNA expression of Bcl2. Additionally, the combination significantly up-regulated and down-regulated the protein levels of AMPK and Akt, respectively. Conclusion: The metformin-lapatinib combination can induce more potent apoptotic death versus each compound individually. The combination may be suggested as a valuable therapeutic intervention in patients with breast cancer. However, additional in vivo studies are necessary to evaluate the clinical use of the combination for induction of apoptosis and its antitumor effects. © 2021 Mashhad University of Medical Sciences. All rights reserved.
Related Docs
1. Metformin: Prevention of Genomic Instability and Cancer: A Review, Mutation Research - Genetic Toxicology and Environmental Mutagenesis (2018)
2. The Role of Her2 Alterations in Clinicopathological and Molecular Characteristics of Breast Cancer and Her2-Targeted Therapies: A Comprehensive Review, Medical Oncology (2022)
3. Effects of Chitosan and Oligochitosans on the Phosphatidylinositol 3-Kinase-Akt Pathway in Cancer Therapy, International Journal of Biological Macromolecules (2020)
4. Targeting Mirnas With Anesthetics in Cancer: Current Understanding and Future Perspectives, Biomedicine and Pharmacotherapy (2021)
5. Impact of Microrna Variants on Pi3k/Akt Signaling in Triple-Negative Breast Cancer: Comprehensive Review, Medical Oncology (2024)
6. Enhancement of Targeted Therapy in Combination With Metformin on Human Breast Cancer Cell Lines, Cell Communication and Signaling (2024)
Experts (# of related papers)
View all Related Experts
Seyed Asadollah Mousavi (1)
Mohammad Ali Mansournia (1)