| Cellular studies |
1. Metformin does not affect PSA expression in LNCaP cells [66,67]. |
| 2. Metformin reduces PSA level in a dose-dependent pattern in two prostate cancer cell lines of LNCaP and C4-2 by upregulating the protein level of small heterodimer partner-interacting leucine zipper resulting in an inhibition of androgen receptor function [68]. |
| 3. Metformin does not affect PSA secretion in LNCaP cells, but may decrease PSA in 22Rv1 cells (p=0.006) [69]. |
| Human studies |
1. Cross-sectional observational studies suggest that metformin use in patients with type 2 diabetes mellitus and without prostate cancer is associated with lower levels of PSA in studies conducted in Canada [70] and in the USA [71]. |
| 2. In a study conducted in China, among patients receiving prostate biopsy, diabetes patients have lower level of PSA but higher grade of prostate cancer than their non-diabetes counterparts [72]. |
| 3. In a US retrospective study, metformin users in patients with prostate cancer presented for radiation therapy may have lower level of PSA, but this does not affect treatment outcomes [75]. |
| 4. Interventional trials conducted in Switzerland [76], Canada [77], and the USA [18] showed a trend of PSA lowering (though not statistically signifcant) after metformin treatment for prosate cancer. |
| Author’s comments |
1. Cellular studies do not show a consistent effect of metformin on PSA expression or secretion. |
| 2. Metformin use may be associated with lower levels of PSA in humans with or without prostate cancer. However, its clinical implications are not clear. |
