Table 2 Key effects of metformin on cancer-associated fibroblasts during cancer therapy

Upregulation of calmodulin-like protein 3 (Calml3)  in CAF isolated from gastric cancer tissues

Suppressed CAF-mediated proclonogenic effect on cancer cells

[178]

Inhibition of CAF-derived interleukin 6 secretion via suppressing of NF-κB signaling in The fibroblast cell line MRC5, and primary fibroblast of ovarian cancer specimen

Alleviation of stromal inflammation in ovarian cancer

[149]

Inhibition of cell growth and induction of apoptosis in OSCC cells by activation of the AMPK pathway, which is followed by downregulation of Bcl-2 expression, upregulation of the Bax/Bcl-2 ratio, and induction of cleaved PARP

Co-culture of NOFs with OSCC inhibited anti-tumor effects of metformin and protected tumor cells from apoptosis through inhibiting the activity of AMPK and PARP. Also, protection of mitochondrial memberane, indicating the supportive effect of fibroblasts in tumor progression

[179]

Interruption of HIF-1α-driven SDF-1 signaling in CAFs obtained from breast cancer tissues

Decreased breast cancer cell invasion

[38]