Influence of metformin on HIF-1 pathway in multiple myeloma
Autor: | Paulina Dudzik, Barbara Ostrowska, Małgorzata Lasota, Dorota Kusior, Kinga A. Kocemba-Pilarczyk, Sonia E. Trojan, Marta Kot |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Angiogenesis
Short Communication Apoptosis Annexin Multiple myeloma Cell Line Tumor medicine Tumor Microenvironment Humans MTT assay Pharmacology Chemistry General Medicine Hypoxia (medical) Metformin HIF-1 pathway Cell Hypoxia multiple myeloma medicine.anatomical_structure Cell culture Cancer research Bone marrow Hypoxia-Inducible Factor 1 medicine.symptom metformin medicine.drug Signal Transduction |
Zdroj: | Pharmacological Reports |
ISSN: | 2299-5684 1734-1140 |
Popis: | Background Multiple myeloma (MM) is defined as plasma cells malignancy, developing in the bone marrow. At the beginning of the disease, the malignant plasma cells are dependent on bone marrow microenvironment, providing growth and survival factors. Importantly, the recent studies pointed hypoxia as an important factor promoting progression of MM. In particular, hypoxia-triggered HIF-1 signaling was shown to promote chemoresistance, angiogenesis, invasiveness and induction of immature phenotype, suggesting that strategies targeting HIF-1 may contribute to improvement of anti-myeloma therapies. Methods The Western Blot and RT-PCR techniques were applied to analyze the influence of metformin on HIF-1 pathway in MM cells. To evaluate the effect of metformin on the growth of MM cell lines in normoxic and hypoxic conditions the MTT assay was used. The apoptosis induction in metformin treated hypoxic and normoxic cells was verified by Annexin V/PI staining followed by FACS analysis. Results Our results showed, for the first time, that metformin inhibits HIF-1 signaling in MM cells. Moreover, we demonstrated the effect of metformin to be mainly oxygen dependent, since the HIF-1 pathway was not significantly affected by metformin in anoxic conditions as well as after application of hypoxic mimicking compound, CoCl2. Our data also revealed that metformin triggers the growth arrest without inducing apoptosis in either normoxic or hypoxic conditions. Conclusions Taken together, our study indicates metformin as a promising candidate for developing new treatment strategies exploiting HIF-1 signaling inhibition to enhance the overall anti-MM effect of currently used therapies, that may considerably benefit MM patients. |
Databáze: | OpenAIRE |
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