Table 3.
Role of PI3K/AKT pathway in esophageal squamous cell carcinoma
| Samples | Cell lines | Drug/phytotherapy | Dose range | Target | Pathway | Function | Refs. |
|---|---|---|---|---|---|---|---|
| ESCC (n = 89), NCLM (n = 58) | TE11 | – | – | miR-21, PTEN | PI3K/AKT | miR-21 through modulation of PTEN/PI3K/AKT pathway promotes invasion/migration, proliferation, cell cycle progression, and resistance to apoptosis of ESCC cells | [47] |
| ESCC (n = 275) | – | – | – | EGFR, ERK1/2, STAT3 | AKT1 | Phosphorylated AKT1 could be involved in poor prognosis in ESCC | [48] |
| ESCC (n = 295) | KYSE180, KYSE140, KYSE150, KYSE30, KYSE410, KYSE450, KYSE510 | – | – |
PAFR, c-myc, survivin, MMP2/9, VEGF |
Dysregulation of PAFR via PI3K/AKT pathway could contribute to the progression of ESCC | [49] | |
| – | EC109 | Vitamin E succinate (VES) | 0–100 µM | Bad, Bcl-2, Caspase-9, p70S6K, 4E-BP1, | PI3K/AKT, mTOR | VES via PI3K/AKT signaling pathway can activate apoptosis in ESCC | [50] |
| – |
KYSE140, KYSE150, KYSE30, KYSE410, KYSE450, KYSE510 |
Dasatinib, cisplatin | 10–500 nM, 0–15 µM |
Src, c-myc, MMP-9, VEGF |
PI3K/AKT, STAT3 | Dasatinib via suppressing the PI3K/AKT and STST3 pathways could improve sensitivity to cisplatin in ESCC cells | [51] |
| - | TE13, Eca109 | – | – |
miR-18a, Cyclin-D1, PTEN, S6K1, pRb-S780 |
PI3K/AKT, mTOR | miR-18a by increasing cyclin-D1 via regulating the PTEN/PI3K/AKT/mTOR axis could promote cell proliferation of ESCC cells | [52] |
| nude mice, 26 pairs of ESCC and nearby non-cancerous tissues | EC109, KYSE30 | – | – | Urokinase plasminogen activator (uPA), GSK-3β | PI3K/AKT, ERK | uPA realized from cancer-associated fibroblasts (CAFs) via the PI3K/AKT and ERK pathways can promote migration, invasion, and proliferation of ESCC cells | [53] |
| nude mice, 20 pairs of ESCC and nearby non-cancerous tissues | Eca109, TE-1, EC109, HET-1A | – | – |
RUNX2, PARP, Caspase-3, GSK-3β |
PI3K/AKT, ERK |
Expression of RUNX2 by activating the PI3K/AKT and ERK pathways could play an oncogenic role in ESCC cells | [54] |
| – | KYSE-30 | Aprepitant | 0–100 µM | NF-kB | PI3K/AKT | SP/NK1R system via the PI3K/Akt/NF-kB pathway could be involved in the pathogenesis of ESCC | [55] |
| – |
EC109, KYSE510, EC9706, NE2, COLO680N, SHEE, EC171, EC18, EC8712 |
– | – |
miR-200b, E-cadherin, Vimentin, ZEB1/2 |
Kindlin-2/integrin β1/AKT | miR-200b via inhibiting the Kindlin-2-integrin β1/AKT pathway could decrease invasion of ESCC cells | [56] |
| 145 pairs of ESCC and adjacent normal tissues | – | – | – | PTEN, P70S6K1, 4E-BP1 | PI3K/AKT, mTOR | PTEN low expression and induction of PI3K/AKT/mTOR signaling can increase ESCC progression | [57] |
| ESCC (n = 68), | TE-8, TE-9, TE-15, Het-1A | – | – | CCL3,CCR5/1, MMP2, MMP9, VEGFA | PI3K/AKT, MEK/ERK | CCL3–CCR5 axis via the MEK/ERK and PI3K/AKT pathways could promote invasion, migration, and angiogenesis of ESCC cells | [58] |
| BALB/c nude mice | Eca109, TE-1 | – | – | HPV16 E6-E7, p75NTR | PI3K/AKT | HPV16 E6-E7 via up-regulating the p75NTR and activating the PI3K/AKT pathway could act as a cancer stem-like cells (CSCs) phenotypes promoter in ESCC cells | [59] |