Abstract
Owing to high blood sugar level and chronic inflammation, diabetes tend to cause the overproduction of free radicals in body, which will damage tissue and cells, reduce autoimmunity, and greatly increase the incidence of tumors. Selenium nanoparticles (SeNPs) exhibit high antioxidant activity with anti-tumor ability. In addition, metformin is considered as a clinical drug commonly for the treatment of stage II diabetes. Therefore, in this study, different functionalized SeNPs combined with metformin were performed to detect the feasibility for cancer therapy. The combination of Tween 80 (TW80)-SeNPs and metformin was found to have a synergistic effect on MCF-7 cells. The mechanism of this synergistic effect involved in the induction of DNA damage by affecting the generation of reactive oxygen species through selenoproteins; the upregulation of DNA-damage-related proteins including p-ATM, p-ATR, and p38; the promotion of p21 expression; and the downregulation of cyclin-dependent kinases and cyclin-related proteins causing cell cycle arrest. Furthermore, the expression of AMPK was affected, which in turn to regulate the mitochondrial membrane potential to achieve the synergistic treatment effect.
Highlights
Cancer, the second leading cause of death worldwide, is increasingly common among patients with chronic diseases such as diabetes (Yan et al, 2021)
We considered whether the differences in the enhanced effects of functional Selenium nanoparticles (SeNPs) combined with metformin on MCF-7 cells were due to the different amounts of different functionalized SeNPs absorbed by cells
Possible synergistic anti-tumor effects of functionalized SeNPs combined with metformin in breast cancer cells were explored, and Tween 80 (TW80)-SeNPs combined with metformin were found to significantly kill MCF-7 cells
Summary
The second leading cause of death worldwide, is increasingly common among patients with chronic diseases such as diabetes (Yan et al, 2021). Diabetes is expected to become the seventh leading cause of death (Ratner, 2012). A higher tumor incidence has been reported in diabetes patients comparing with people without diabetes (Monami et al, 2011; Luo et al, 2020; Zhang et al, 2020; Park and Sandler, 2021). Breast cancer is among the cancers that are complicated by diabetes; its mortality rate is high in diabetes patients (Shelby et al, 2020; Park and Sandler, 2021). The treatment of tumor patients with complex needs must take into account the interactions and contraindications among different diseases
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