Objective: To study the pharmacological mechanism of ethanol extract of infructescence of Platycarya strobilacea (EPS) treatment on CNE1 and CNE2 cells in nasopharyngeal carcinoma (NPC).Method: NPC cells (CNE1 and CNE2) were taken as the research objects and treated with 0 (blank group)

0.25

0.5

1.0

1.5

2.0 g·L-1 for 24 h. The effect of EPS on viability of CNE1 and CNE2 cells were detected by (4

5-dimethyl-2-thiazolyl)-2

5-diphenyl-2-H-tetrazolium bromide (MTT) assay. After CNE1 and CNE2 cells were treated with 1.0 g·L-1 EPS for 24 h

the morphological changes of the cells were observed by inverted microscope. The changes of organelles were observed by transmission electron microscopy (TEM). Flow cytometry was used to detect the apoptosis of CNE1 and CNE2 cells induced by EPS. The differential genes in the cells were detected by nucleotide high throughput sequencing

and the expression levels of HRas proto-oncogene (HRAS)

extracellular regulated protein kinase 1/2 (ERK1/2) and c-Fos proto-oncogene (c-Fos) proteins were detected by Western blot (WB).Result: As compared with blank control group

EPS could significantly inhibit the growth of CNE1 and CNE2 cells in a dose-dependent manner (P<0.05).After being treated with EPS

CNE1 and CNE2 cells showed a large number of vacuoles

and the vacuoles became confluent with each other and became larger and larger. Finally

the cell membrane ruptured and the nucleus did not change obviously. EPS could not promote CNE1 and CNE2 cells apoptosis and NPC cells had obvious characteristic methuosis changes in the observation under phase contrast microscope. RNA sequencing results showed that renin-angiotensinsystem (RAS)/mitogen-activated protein kinase (MAPK) signaling pathway was involved. WB results showed that as compared with the blank control group

EPS could reduce the protein expression levels of HRAS

c-Fos and ERK1/2

but increase the protein expression levels of p-ERK1/2 (P<0.05).Conclusion: EPS can induce methuosis death in human nasopharyngeal carcinoma cells CNE1 and CNE2 through regulating RAS/MAPK signaling pathway

thus leading to confluence of cells and resulting in a large number of vacuoles.