Table 1 Synergistic effect in different type of cancer via combined treatment of chemotherapy and HIF inhibitor
Cell | Cell line | Agent associated with HIF | Chemotherapy or Target therapy | Synergistic effects | Reference of study and 2D structure |
|---|---|---|---|---|---|
Brain | Glioma | SN38: active metabolite of irinotecan
| Decreases VEGF | PubChem CID: 104842 URL: https://pubchem.ncbi.nlm.nih.gov/compound/104842 [57] | |
Glioma (D54MG) | HIF-1α knockdown | Temozolomide
| Caspase activation for the cell death | PubChem CID: 5394 URL: https://pubchem.ncbi.nlm.nih.gov/compound/Temozolomide [58] | |
Glioblastoma (U-87) | HIF-1α knockdown | Cisplatin
| No synergistic effect | PubChem CID: 5702198 URL: https://pubchem.ncbi.nlm.nih.gov/compound/5702198 [59] | |
Head and Neck | Xenografts model (SQ20B) | Erlotinib: EGFR inhibitor
| Cisplatin
| Decreases VEGF and modulates tumor microenvironment | (E)PubChem CID: 176870 URL: https://pubchem.ncbi.nlm.nih.gov/compound/176870 [60] |
Lung | Small cell lung cancer cells | NVP-ADW742: IGF-I receptor kinase inhibitor
| Etoposide
| Eliminates PI3K-Akt activity | (N)PubChem CID: 9,825149 URL: https://pubchem.ncbi.nlm.nih.gov/compound/9825149 (E)PubChem CID: 36462 URL: https://pubchem.ncbi.nlm.nih.gov/compound/Etoposide [61] |
Non-small cell lung cancer cells | Panobinostat: HDAC inhibitor
| Cisplatin
| Induces apoptosis, Activates caspases and PARP cleavage | (P)PubChem CID: 6918837 URL: https://pubchem.ncbi.nlm.nih.gov/compound/6918837 [62] | |
Cells and xenograft model (A549) | Acriflavine
| Prevents the formation of HIF-1α/β dimers | (A)PubChem CID: 443101 URL: https://pubchem.ncbi.nlm.nih.gov/compound/443101 [63] | ||
Cells and xenograft model (H460) | Oroxylin A
| Binds to HIF-1α bHLH-PAS domain | (O)PubChem CID: 5320315 URL: https://pubchem.ncbi.nlm.nih.gov/compound/5320315 [64] | ||
Ovary | Cells | NSC606985: Campothecin analog
| Cisplatin
| Antagonizes the accumulation of HIF-1α | (N)PubChem CID: 354677 URL: https://pubchem.ncbi.nlm.nih.gov/compound/354677 [65] |
Cells (OVCAR10 and SKOV-3) | RAD001 (everolimus)
| Enhances cisplatin-induced apoptosis | (R)PubChem CID: 46930999 URL: https://pubchem.ncbi.nlm.nih.gov/compound/46930999 [66] | ||
Cells | Noscapine
| Degrades cobalt-stabilized HIF-1α | (N)PubChem CID: 275196 URL: https://pubchem.ncbi.nlm.nih.gov/compound/275196 [67] | ||
Colorectal | Cells | Acriflavine
| Doxorubicin
| Suppresses HIF-1 and the DNA replication | (D)PubChem CID: 31703 URL: https://pubchem.ncbi.nlm.nih.gov/compound/Doxorubicin [68] |
Cells (HT29) | L-carnosine
| 5-FU
| Decreases multidrug resistant protein MDR1-pg | (L)PubChem CID: 439,224 URL: https://pubchem.ncbi.nlm.nih.gov/compound/439224 [5] PubChem CID 3385 URL: https://pubchem.ncbi.nlm.nih.gov/compound/5-Fluorouracil [69] | |
Cells (SW1116) | Endostar
| Oxaliplatin
| Reduces HIF-2α and CXCR4 levels | (E)PubChem CID: 187888 URL: https://pubchem.ncbi.nlm.nih.gov/compound/187888 (O)PubChem CID: 43805 URL: https://pubchem.ncbi.nlm.nih.gov/compound/43805 [70] | |
xenograft model | IDF-11774
| 5-FU
| Restores 5-FU sensitivity in chemoresistant tumor | Pubchem CID: 71542096 URL: | |
Liver | Cells (Hep3B) | Melatonin
| Sorafenib
(S)PubChem CID: 216239 URL: | Reduces HIF-1α mitophagy expression | (M)PubChem CID: 896 URL: https://pubchem.ncbi.nlm.nih.gov/compound/896 [71] |
Cells (HepG2) | 2-Methoxyestradiol (2ME2)
| Induces cell apoptosis Inhibits tumor angiogenesis | [2] PubChem CID: 66414 URL: https://pubchem.ncbi.nlm.nih.gov/compound/66414 [72] | ||
Cells | PT-2385: HIF-2α inhibitor
| Suppresses HIF-2α Increases androgen receptor | (P)PubChem CID: 91754484 URL: https://pubchem.ncbi.nlm.nih.gov/compound/91754484 [73] | ||
Breast | TNBC cells (Rb-positive) | Palbociclib: CDK4/6 inhibitor
| BYL719: PI3K/mTOR inhibitors
| Inhibits both CDK4/6/Rb/myc and PI3K/ mTOR signaling | (P)PubChem CID: 5330286 URL: https://pubchem.ncbi.nlm.nih.gov/compound/5330286 (B)PubChem CID: 56649450 URL: https://pubchem.ncbi.nlm.nih.gov/compound/56649450 [13] |
Paclitaxel
| Downregulates the E2F target c-myc Reduces HIF-1α and GLUT1 expression | (P)PubChem CID: 36314 URL: https://pubchem.ncbi.nlm.nih.gov/compound/36314 [74] | |||
Cells and xenograft model (MCF-7) | Zoledronic acid (ZOL)
| Fulvestrant
| Inhibits ERK 1/2 phosphorylation | (Z)PubChem CID: 68740 URL: https://pubchem.ncbi.nlm.nih.gov/compound/68740 (F)PubChem CID: 104741 URL: https://pubchem.ncbi.nlm.nih.gov/compound/104741 [75] | |
Xenograft model | CRLX101: TOPO-1 and HIF-1α inhibitor
| Bevacizumab | Impedes the induction of both HIF-1α and cancer stem cell self-renewal | (C)PubChem CID: 184196 URL: https://pubchem.ncbi.nlm.nih.gov/compound/184196 [76] | |
Pancreas | Cells | PX-478
| Gemcitabine
(G)PubChem CID: 60750 URL: | Elicits exposure of CRT Release of HMGB1 and ATP | (P)PubChem CID: 11234794 URL: https://pubchem.ncbi.nlm.nih.gov/compound/11234794 [77] |
Cells | FRAX597: PAK1 selective inhibitor
| Inhibits HIF-1α and AKT activity | (F)PubChem CID: 70934541 URL: https://pubchem.ncbi.nlm.nih.gov/compound/70934541 [78] | ||
Cells (PANC-1) | HS-173: PI3K inhibitor
| Sorafenib
| Induces G2/M arrest Increases apoptosis | (H)PubChem CID: 52936849 URL: https://pubchem.ncbi.nlm.nih.gov/compound/hs-173 [79] | |
