Table 3.
Hypoxia and sorafenib resistance in HCC cells.
| HIFs after sorafenib treat in HCC | Cell line/animal models | Target | Reference |
|---|---|---|---|
| HIF-1α↑ | HepG2, Huh7/– | AKT↑ | (114) |
| HIF-1α↑ | HepG2, SMMC-7721, BEK-7402, Hep3B, Huh-7/BALB/c nude mice subcutaneous HCC model | – | (80) |
| HIF-2α↑HIF-1α↓ | HepG2, Huh7/BALB/c mice subcutaneous HCC model | VEGF↑cyclinD1↑LDHA↓ | (109) |
| HIF-1α↑ | –/Kunming mice subcutaneous HCC model | AKT↑ | (121) |
| HIF-2α↑HIF-1α↓ | HepG2, Bel-7402, Huh-7, SMMC-7402/BALB/c mice subcutaneous HCC model | PCNA↑β-catenin↑ C-Myc↑ | (122) |
| HIF-1α↑ | HepG2, Huh7/Athymic nude‐Foxn1 subcutaneous HCC model | AMPK↓AKT↑ | (112) |
| HIF-1α↑ | Huh7/BALB/c mice subcutaneous HCC model and tail vein inoculation model | Galectin↑mTOR↑ | (113) |
| HIF-1α↑ | Hep3B/– | mTOR↑ | (123) |
| HIF-1α↑ | LM3, SMMC-7721, Bel-7402, HepG2/nude mice subcutaneous HCC model | PPAR-γ↑PKM2↑ | (124) |
| HIF-2α↑ | MHCC97H/BALB/c mice subcutaneous HCC model and orthotopic model | TIP30↓EMT↑ | (117) |
| HIF-1α↑ | LM3, SMMC-7721, Hep3B, Bel-7402, Huh-7, LO2/BALB/c mice subcutaneous HCC model | GULT1↑HK2↑ | (125) |
| HIF-1α↑ | LM3, SMMC-7721, Bel-7402, Huh-7, HepG2, LO2/BALB/c mice subcutaneous HCC model | PKM2↑ | (126) |
| HIF-2α↑HIF-1α↑ | HepG2/– | BNIP3↓ | (118) |
| HIF-1α↑ | Huh7/BALB/c nude mice subcutaneous HCC model | 14-3-3η↑ | (49) |
| HIF-2α↑HIF-1α↑ | HepG2, Hep3B, SK-Hep-1/BALB/c mice subcutaneous HCC model | ATPaseα3↑ | (127) |
| HIF-2α↑ | HepG2, SKhep1/BALB/c mice subcutaneous HCC model and tail vein inoculation model | androgen receptor↓ | (128) |
| HIF-1α↑ | HepG2, Hep3B, PLC/5, SK-Hep-1/BALB/c mice subcutaneous HCC model, tail vein inoculation model and orthotopic model | VEGF↑MDR1↑P-gp↑ GULT1↑NF-κB↑ | (129) |
| HIF-2α↑HIF-1α↓ | HepG2/BALB/c mice subcutaneous HCC model | TGF-α↑EGFR↑ | (107) |
| HIF-1α↑ | Hep3B, HepG2, PLC/PRF/5, HEK 293T/BALB/c mice orthotopic model | RIT1↑ | (119) |
| HIF-1α↑ | SK-Hep-1, SMMC-7721, HepG2, Huh7, MHCC-97H, LM3/– | PFKFB3↑ | (120) |