Objective:

2

To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration.

Methods:

2

HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay

and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF)

EGF receptor (EGFR)

phosphatidylinositol 3-kinase (PI3K)

protein kinase B (AKT)

mammalian target of rapamycin (mTOR)

and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot

respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR.

Results:

2

HSYA (800 μmol/L) significantly promoted HaCaT cell proliferation and migration (

P

<

0.05 or

P

<

0.01). It also increased the mRNA and protein expression levels of HBEGF

EGFR

PI3K

AKT

mTOR and HIF-1α

and increased the phosphorylation levels of PI3K and AKT (

P

<

0.05 or

P

<

0.01). Furthermore

HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (

P

<

0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF

EGFR

PI3K

AKT

mTOR and HIF-1α (

P

<

0.05). HSYA inhibited the circ_0084443 expression

further antagonized the inhibition of circ_0084443 on HBEGF

EGFR

PI3K

AKT

mTOR and HIF-1α

and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (

P

<

0.05 or

P

<

0.01). However

HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (

P

>

0.05).

Conclusion:

2

HSYA played an accelerative role in HaCaT cell proliferation and migration

which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways

and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.