Table 7.

Role of PI3K/AKT pathway in cutaneous squamous cell carcinoma

Type of Diseases	Samples	Cell Lines	Drug/ phytotherapy	Dose range	Target	Pathway	Function	Refs.
Skin cancer	Female ICR mice	–	a-mangostin	5 and 20 mg/kg	IL-4/10/18, IL-1β, Bax, Caspase-3, Bcl-2, LC3-II/I, Beclin-1	PI3K/AKT, mTOR	a-Mangostin by regulating PI3K/AKT/mTOR pathway could inhibit DMBA/TPA-induced skin cancer	[115]
Cutaneous squamous cell carcinoma (CSCC)	–	SCC, A431	Lapatinib	0–5 μM	Caspase-8, Bcl-2, EGFR, N-cadherin, Vimentin	WNT/β-catenin, PI3K/AKT, mTOR, ERK1/2	Lapatinib via the WNT/ERK/PI3K/AKT axis could suppress EMT	[116]
Skin cancer	–	SKMEL-5	Lactucopicrin	0–30 μM	Bax, Bcl-2	PI3K/AKT, mTOR	Lactucopicrin via inhibiting the PI3K/AKT/mTOR pathway exerted anticancer effects on skin cancer cells	[103]
Skin carcinoma	–	A549, A431, PaCa-2, PC-3, MCF-7, SNU-5, HTB-39	caffeic acid n-butyl ester (CAE)	0–40 μM	Bax, Bcl-2	PI3K/AKT, mTOR	CAE via induction of apoptosis and inhibition of the PI3K/AKT/mTOR pathway could reduce proliferation of skin cancer cells	[119]
CSCC	–	HaCaT, cSCC, A431, HSC-5, SCC-12, SCL-1	–	–	miR-451a, PDPK1	PI3K/AKT	miR-451a via PDPK1-mediated PI3K/AKT modulation could prevent CSCC progression	[117]
CSCC	Female nude mice	cSCC, A431	–	–	LINC00520, EGFR, VEGF, MMP-2/9	PI3K/AKT	lncRNA LINC00520 via inactivating the PI3K/AKT pathway by decreasing EGFR could prevent the progression of CSCC	[118]
CSCC	CSCC tissues (n = 11), normal skin tissues (n = 4)	cSCC, NHEK HaCaT, A431, SCL-1	–	–	Kynureninase (KYNU)	PI3K/AKT	Downregulation of KYNU could restrain CSCC proliferation and repress the PI3K/AKT pathway	[120]
CSCC	–	SCC13, A431	High mobility group box 1 (HMGB1)	0–100 ng/mL	p42/44, p38	PI3K/AKT, MAPK	HMGB1 via the PI3K/AKT and MAPK pathways can influence tumor metastasis	[121]