Table 2.
Role of PI3K/AKT pathway in laryngeal squamous cell carcinoma
| Samples | Cell lines | Drug/phytotherapy | Dose range | Target | Pathway | Function | Refs. |
|---|---|---|---|---|---|---|---|
| – | AMC-HN-8, HuLa-PC | Mukonal | 0–100 µM | – | PI3K/AKT, MEK, ERK | Mukonal by affecting activity of the PI3K/AKT and MEK/ERK pathways and by promoting apoptosis and G2/M cell cycle arrest could inhibit the migration/invasion and proliferation of LC cells | [20] |
| BALB/c nu/nu |
Hep-2, TU212, HBE |
Dehydrocostus Lactone (DHL) | 0–10 µg/mL |
Bcl-2, Bax, Bad, p53, p21, PTEN Waf1/Cip1, Cyclin-D1, MMP-2/9, Caspase-12/9/3 |
PI3K/AKT | DHL by stimulating endoplasmic reticulum (ESR) stress and inhibiting PI3K/AKT/Bad signaling pathway could inhibit cell proliferation | [21] |
| LSCC (n = 137), non-cancerous laryngeal mucosa (n = 100) | – | – | – | FGFR1, FGFR3 | PI3K/AKT | FGFR1 and FGFR3 via targeting the PI3K/AKT pathway could be involved in the invasiveness and prognosis of LSCC | [22] |
|
LSCC (n = 110), laryngeal severe dysplasia (n = 30) |
AMC-HN8, TU212, TU686 | – | – | FADS1, S6K1 | AKT/mTOR | Overexpression of FADS1 via activating the AKT/mTOR pathway could promote LSCC growth and migration/invasion | [23] |
|
Cohort, BALB/C nude mice |
Tu 177/Cis, HOK, 293 T, MRC-5, FD-LSC-1/Cis |
Cisplatin | 0–25 µg/mL | miR-145-5p, circPARD3, p62, LC3B-I/II, PRKCI | AKT/mTOR | CircPARD3 through the miR-145-5p/PRKCI/AKT/mTOR axis could promote proliferation, migratory potential, invasion, and chemoresistance | [24] |
| LSCC (n = 53), ANM (n = 53), male BALB/C nude mice |
FD-LSC-1, TU-177 |
– | – |
SKA3, PLK1, HK2, PFKFB3, PDK1, PTEN, c-Myc |
AKT | SKA3 via interacting with PLK1 to activate the AKT pathway by up-regulating glycolysis level could suppress the chemoresistance and proliferation of LSCC | [25] |
| – | Hep-2 | – | – | SHIP2, p21, p27, Caspase-3 | PI3K/AKT | Knockdown of SHIP2 could inactive the PI3K/AKT pathway. Hence, it could be involved in radiosensitivity of LSCC | [26] |
| BALB/cA nu/nu | AMC-HN-8 | miR-145 | PI3K/AKT | miR-145 via the PI3K/AKT axis can inhibit the proliferation and growth of LSCC | [27] | ||
| 16 pairs of LSCC and adjacent normal tissues | AMC‐HN‐8, TU212 | – | – |
MMP-2/3, NF-kB, E‐cadherin, Vimentin, Occluding, N‐cadherin, |
PI3K/AKT | Knockdown of MMP2/3 via the PI3K/AKT/NF-kB axis can affect proliferation and migration of LSCC cells | [28] |
| 46 pairs of LSCC and adjacent normal tissues | Hep-2, TU212, AMC-NH-8, TU686 | – | – |
MEOX2, c-Myc, Caspase-3, XIAP |
PI3K/AKT | MEOX2 through inhibiting the PI3K/AKT pathway can suppress cancer cell viability and apoptosis | [29] |
| 20 pairs of LSCC and adjacent normal tissue | Hep-2 | – | – | Tra2β, Bax, Bcl-2, Caspase-3 | PI3K/AKT | Silencing of Tra2β via inhibiting the PI3K/AKT pathway leads to suppression of proliferation, invasiveness, and migration of malignant cells | [30] |
| 32 pairs of LSCC and adjacent normal tissues |
TU-177, TU686, TU212, AMC-HN-8, NHOKs |
Curcumin | 0–40 µM | miR-145 | PI3K/AKT, mTOR | Curcumin via up-regulation of miR-145 and inhibiting PI3K/AKT, mTOR pathway could suppress LSCC progression | [31] |
| 65 pairs of LSCC and adjacent normal tissues | Hep-2 | – | – | miR-138, EZH2 | PI3K/AKT | miR-138 via inhibiting the expression of EZH2 and PI3K/AKT pathway had a suppressive role in LSCC proliferation | [32] |
| 40 pairs of LSCC and adjacent normal tissues | SNU899, SNU46 | – | – | miR-375, miR-205, PTEN, E-cadherin, Vimentin, Snail2 | AKT | miR-375/205 via AKT-mediated EMT could be involved in the invasion and migration of LSCC | [33] |
| 10 pairs of LSCC and adjacent normal tissues |
Hep-2, AMC-HN-8, HaCaT |
– | – |
miR-132, FOXO1, p21, p27, Cyclin-D1 |
PI3K/AKT | miR-132 by up-regulating FOXO1 and activating the PI3K/AKT pathway could act as an oncogene in LSCC cell proliferation and growth | [34] |
| – |
D-Hep2, T-Hep2 |
– | – | AURKA, FAK, P130, E2F4 | PI3K/AKT | AURKA via the FAK/PI3K/AKT axis could promote invasion and migration of LSCC tumor cells | [35] |
| – | SNU-46 | – | – | DJ-1, PTEN | PI3K/AKT, mTOR | Overexpression of DJ-1 via activating the PI3K/AKT/mTOR pathway could accelerate proliferation rate, migration, and invasion of LSCC cell | [36] |
| 85 pairs of LSCC and adjacent normal tissues | Hep-2 | – | – | TSLC1, Bcl-2, p21, Caspase-3, Bax, MMP-2/9 | AKT | Overexpression of TSLC1 via AKT signaling could reduce and suppress proliferation and invasiveness and induce apoptosis of LSSC cells | [37] |