Journal of the Egyptian National Cancer Institute · 2026
Metformin enhances methylene blue-mediated photodynamic therapy in oral squamous cell carcinoma.
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Osman Mohamed A, Sharaky Marwa, Abdel-Fattah Hesham, Safaan Ali M
Аннотация
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck region with relatively low survival rate and response and high resistance to treatment. Tongue and floor of the mouth are the most commonly involved sites. New therapies for oral squamous cell carcinoma (OSCC) treatment are still required. An attractive option for the treatment of OSCC is the use of photodynamic therapy (PDT). Considering metformin's potential to reduce cancer risk and inhibit proliferation, therefore the present study aims to evaluate its ability to potentiate the methylene blue-mediated photodynamic effect against the growth of tongue cancer cells in vitro and the possible molecular mechanisms of action involved.
METHODS: Cytotoxic activity of metformin (MF) and/or Methylene blue (MB)+laser light (L) against the growth of HNO97 tongue cells was determined using the sulforhodamine (SRB) method. Several protein expressions were determined using ELISA kits include mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase 8.
RESULTS: Laser light at different energy per surface area induced inhibition in the surviving fraction of HNO97 cells, while in presence of MB (10 µg/ml for 4 h.), the surviving fractions showed more inhibition. Addition of MF (1000 µg/ml, for 24 h.) to MB + L induced significant 51 and 89% inhibition of cell survival at energy level of 45 and 337.5 J/cm2, respectively. Addition of Metformin to MB-photodynamic therapy also increased the expression AMPK and decrease the expression of mTOR at the protein level. Moreover there were increase in Bax expression and decrease in Bcl2 expression with significant increase in caspase 8 expression at the protein level.
CONCLUSION: Such combined treatment showed promising synergistic interaction via several molecular pathways, which is well tolerated and readily applicable strategy to improve the therapeutic outcome of PDT in cancer cell treatment.
METHODS: Cytotoxic activity of metformin (MF) and/or Methylene blue (MB)+laser light (L) against the growth of HNO97 tongue cells was determined using the sulforhodamine (SRB) method. Several protein expressions were determined using ELISA kits include mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase 8.
RESULTS: Laser light at different energy per surface area induced inhibition in the surviving fraction of HNO97 cells, while in presence of MB (10 µg/ml for 4 h.), the surviving fractions showed more inhibition. Addition of MF (1000 µg/ml, for 24 h.) to MB + L induced significant 51 and 89% inhibition of cell survival at energy level of 45 and 337.5 J/cm2, respectively. Addition of Metformin to MB-photodynamic therapy also increased the expression AMPK and decrease the expression of mTOR at the protein level. Moreover there were increase in Bax expression and decrease in Bcl2 expression with significant increase in caspase 8 expression at the protein level.
CONCLUSION: Such combined treatment showed promising synergistic interaction via several molecular pathways, which is well tolerated and readily applicable strategy to improve the therapeutic outcome of PDT in cancer cell treatment.