Table 5 Synergistic effect via combination of metformin and chemotherapy, target therapy, or immune therapy

Vitamin C

BAY 87–2243

Inhibits the expression levels of VEGF via HIF‑1α‑dependent and AKT‑dependent pathways

Lens epithelial cells

[153]

PubChem CID: 54670,067, 67377767

URL:

https://pubchem.ncbi.nlm.nih.gov/compound/54670067

https://pubchem.ncbi.nlm.nih.gov/#query=67377767

Cisplatin

Metformin

Inhibits the NF-κB/ HIF-1α signal axis

Oral squamous cell carcinoma cells

[148, 154]

PubChem CID: 5702198

URL:

https://pubchem.ncbi.nlm.nih.gov/compound/5702198

5‑FU

Metformin

Targets the AMPK/mTOR/HIF‑1α/P‑gp and MRP1 pathways to reverse MDR

Hepatocellular carcinoma cells

[149]

PubChem CID: 3385

URL:

https://pubchem.ncbi.nlm.nih.gov/compound/3385

Downregulates of HIF-1α and mTOR

Oral squamous cell carcinoma

[150]

Doxorubicin

Metformin

Inhibits HIF-1α and P-glycoprotein (Pgp) expression

Breast cancer cells (MCF7/ADR)

[151]

PubChem CID: 31703

URL:

https://pubchem.ncbi.nlm.nih.gov/compound/31703

Bevacizumab

Metformin

Inhibits VEGF, CD34, and HIF-1α expression

Ovarian cancer cells (SKOV3)

[152]

PD-1/ PD-1 antibodies (J43)

Metformin

Decreases tumor hypoxic status

Melanoma (Mouse: B16)

PubChem

CID:4091

URL:

https://pubchem.ncbi.nlm.nih.gov/compound/4091

[155]

Colon carcinoma (Mouse:MC38)

CTLA-4/ CTLA-4 mAb (Cat#BE0032;RRID:AB_1107798)

Metformin

Decreases tumor hypoxic status

Breast cancer (Mouse: 4T1-Luc2

Human: MDA-MB-231, MDA-MB-361, BT-549)

[156]

Lung cancer (Human:H1975, H358)

Colon cancer (Human: RKO, CT26)

Melanoma (Mouse: B16-F10)