Prostate cancer (PrCa) is the most common male cancer in Western countries
Radiotherapy (RT) is the main treatment for all stages of prostate cancer, but prostate tumors are resistant to this treatment
Increasing the radiation dose can improve local disease control, but it can cause bladder and intestinal toxicity
Therefore, there is a need for methods that can increase the sensitivity of radiotherapy
Anti- diabetic drugs metformin (MET) and aspirin metabolite salicylate (SAL) can activate AMP protein kinase (AMPK) and inhibit adipogenesis (DNL) and mammalian rapamycin (mTOR) pathways, and can reduce in vitro Proliferation of PrCa
Recently, researchers from Canada published an article in "Transl Oncol", investigating whether MET+SAL treatment can enhance PrCa tumor suppression and improve the response to RT
Investigate whether MET+SAL treatment can enhance the PrCa tumor suppression effect and improve the response to RT.
The researchers used androgen-sensitive (22RV1) and resistant (PC3, DU-145) PrCa cells and PC3 xenografts to investigate whether MET+SAL treatment is better than MET or SAL alone in inhibiting PrCa cells and Tumor activity
The mechanism of action was investigated by analyzing signal pathways, mitochondrial respiration and DNL activity determination
It was found that PrCa cells are resistant to clinical doses of MET
MET+SAL treatment can produce synergistic anti-proliferative activity at clinical doses and enhance the anti-proliferative effect of RT
The above effects are related to the inhibition of oxygen consumption rate (OCR), the activation of AMPK, the inhibition of acetyl-CoA carboxylase (ACC)-DNL and mTOR-p70s6k/4EBP1 and HIF1α pathways
MET+SAL reduces the growth of non-radiotherapy tumors and enhances the effect of RT
Metformin + salicylic acid can inhibit tumor growth and DNA replicationMetformin + salicylic acid can inhibit tumor growth and DNA replication
In summary, MET+SAL treatment can inhibit the proliferation of PrCa cells and tumor growth, and enhance the response to RT at clinical doses
MET and SAL are widely used safely and cheaply.
Their data supports further investigation in PrCa clinical trials
Original source:Original source:
Evangelia E Tsakiridis, Lindsay Broadfield, Katarina Marcinko et al.
Combined metformin-salicylate treatment provides improved anti-tumor activity and enhanced radiotherapy response in prostate cancer; drug synergy at clinically relevant doses .
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