Table 1.
Target | Action | Outcome | Model Used | Reference(s) |
---|---|---|---|---|
MAPKs | p-JNK↓; p-ERK↑; p-P38↑ | Apoptosis↑; proliferation↓; | A549; A549/Taxol | 22, 23 |
MKP-1↓ | Reversing antimetastatic effect of PPARγ agonist rosiglitazone | H441 | 24 | |
ERK2↑; caspase 3 and 8↑ | Apo2L/TRAIL-induced apoptosis sensitization | A549; NCI-H358; Calu1; SkLu1 | 27 | |
NF-κB | p65 transactivation↓ | TRAIL-induced apoptosis↑ | A549 | 26 |
IKBα phosphorylation and degradation↓ NF-κB nuclear translocation↓ | Incidence↓ | H460; H460; PC3; FEN1 E160D mice; LLC-grafted mice | 29 | |
TRAIL-induced NF-κB transcriptional activity↓ | Sensitive to TRAIL-induced apoptosis↑ | A549; NCl-H1299 | 30 | |
NF-κB↓; NF-κB-regulated drug-resistant gene expression↓ | Reversal of the Taxol resistance | A549; A549/Taxol | 51 | |
HA-CD44/RHAMM | ERK↓; Akt↓; EGFR↓ | Growth and survival↓ | A549; H520; H1299; H1650; H1975; A549 xenograft in male nude mice | 34 |
Potential EGFR antagonist | Proliferation↓ | Molecular dynamics simulation; H2347 | 35 | |
miRNA | 126 miRNAs↑; 101 miRNAs↓ | Altering miRNA expression profile | H358 | 43 |
miR-21↓; PTEN protein↑; caspase 3 and 9↑ | Proliferation↓; apoptosis↑ | PC-9 | 45, 46 | |
FAK | p130Cas↓; Src↓; less metastatic colonization compared to control mice | Migration, invasion, and metastasis↓ | H460; A549; H358; H358 xenograft in NOD SCID γ mice | 43 |
PI3K/Akt | p-Akt↓; p-GSK-3β↑; Bax↑; caspases↑; Bcl-2↓ | Proliferation↓; S-phase arrest | A549; A549/Taxol | 23 |
p-Akt↓ | Cytotoxicity | H1299, H460 | 36 | |
Tumor-related protein expression | Dysregulation of tumor-related protein | Apoptosis↑; G2/M phase arrest | A549 (ITRAQ-based proteomics analysis) | 52 |
Keap1/Nrf2 | Nrf2 transcriptional activity↓ | Chemoresistance to antitumor drugs↓ | LLC; Nrf2-KD; 3LL and Nrf2-KD xenograft in C57BL/6 mice | 53 |
Wnt | Epigenetic modifications to histone H3; WIF1 | Growth↓ | A549; H460; H358; H1299; E160D mice; A549 and H460 xenograft in NOD SCID γ mice | 55 |
WIF1 demethylation | Apoptosis↑; migration↓ | A549; H460 | 57 |
MAPKs, mitogen-activated protein kinases; JNK, c-Jun N-terminal kinase; ERK, extracellular signal-regulated kinase; MKP-1, kinase phosphatase-1; Apo2L/TRAIL, Apo2L/tumor necrosis factor-related apoptosis-inducing ligand; Akt, protein kinase B; LLC, the Lewis lung cancer; EGFR, epidermal growth factor receptor, PTEN, phosphatase and tensin homolog; FAK, focal adhesion kinase; MMP14, matrix metalloproteinase 14, iTRAQ, isobaric tags for relative and absolute quantitation; Nrf2, nuclear factor erythroid 2-related factor 2; WIF1, Wnt inhibitory factor 1; ↑, activation/upregulation; ↓, suppression/downregulation.