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Enhancement of targeted therapy in combination with metformin on human breast cancer cell lines
Ghazal Mahmoudi1, Yahya Ehteshaminia2, Parviz Kokhaei3
1Student Research Committee, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
Background:
Breast cancer remains a primary global health concern due to its limited treatment options, frequent disease recurrence, and high rates of morbidity and mortality. Thereby, there is a need for more effective treatment approaches. The proposal suggests that the combination of targeted therapy with other antitumoral agents could potentially address drug resistance. In this study, we examined the antitumoral effect of combining metformin, an antidiabetic drug, with targeted therapies, including tamoxifen for estrogen receptor-positive (MCF-7), trastuzumab for HER2-positive (SKBR-3), and antibody against ROR1 receptor for triple-negative breast cancer (MDA-MB-231).
Methods:
Once the expression of relevant receptors on each cell line was confirmed and appropriate drug concentrations were selected through cytotoxicity assays, the antitumor effects of both monotherapy and combination therapy on colony formation, migration, invasion were assessed in in vitro as well as tumor area and metastatic potential in ex ovo Chick chorioallantoic membrane (CAM) models.
Results:
The results exhibited the enhanced effects of tamoxifen when combined with targeted therapy. This combination effectively inhibited cell growth, colony formation, migration, and invasion in vitro. Additionally, it significantly reduced tumor size and metastatic potential in an ex ovo CAM model.
Conclusions:
The findings indicate that a favorable strategy to enhance the efficacy of breast cancer treatment would be to combine metformin with targeted therapies.
Insights
Combining metformin with targeted therapies like tamoxifen shows enhanced breast cancer treatment efficacy. This approach effectively inhibits tumor growth, migration, and metastasis in preclinical models.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Breast cancer presents significant treatment challenges, including drug resistance, recurrence, and mortality.
- Novel therapeutic strategies are crucial for improving patient outcomes.
- Combining targeted therapies with existing drugs may overcome resistance mechanisms.
Purpose of the Study:
- To investigate the combined antitumoral effects of metformin with specific targeted therapies in different breast cancer subtypes.
- To evaluate the efficacy of metformin-tamoxifen, metformin-trastuzumab, and metformin-anti-ROR1 antibody combinations.
Main Methods:
- Confirmed receptor expression and determined drug concentrations via cytotoxicity assays for MCF-7, SKBR-3, and MDA-MB-231 cell lines.
- Assessed in vitro effects on colony formation, migration, and invasion for monotherapy and combination treatments.
- Evaluated ex ovo Chick chorioallantoic membrane (CAM) models for tumor area and metastatic potential.
Main Results:
- Metformin combined with tamoxifen demonstrated enhanced antitumoral effects.
- The combination significantly inhibited breast cancer cell growth, colony formation, migration, and invasion in vitro.
- Ex ovo CAM models showed reduced tumor size and metastatic potential with the combination therapy.
Conclusions:
- Combining metformin with targeted therapies is a promising strategy to enhance breast cancer treatment efficacy.
- This approach holds potential for overcoming drug resistance and improving therapeutic outcomes.
- Further research into metformin-based combination therapies is warranted for clinical application.
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