Serum Starvation Induces Matrix Metalloproteinase 9 Expression in Nasopharyngeal Carcinoma Cells Through the ERK-AP1 Pathway In Vitro

Abstract

Background/aim: Although clinical medicine has significantly progressed in treating nasopharyngeal carcinoma (NPC) in recent years, many patients still have poor prognoses due to distant metastasis. It is still relatively unclear why NPC has a highly metastatic ability. Especially whether the tumor microenvironment affects the invasion and metastasis of NPC still needs to be cleared. In this study, serum starvation was used to simulate nutrient deficiency in the tumor microenvironment to explore whether nutrient deficiency affects the malignancy of NPC cells.

Materials and methods: Semiquantitative reverse transcription-polymerase chain reaction, ELISA, immunoblotting assay, reporter gene assay, and Matrigel invasion assay were carried out.

Results: Under serum starvation, NPC cells could induce the mRNA expression and protein secretion of matrix metalloproteinase 9 (MMP9). The ERK-AP1 pathway was activated under serum starvation in NPC cells, resulting in the expression of MMP9. In contrast, treatment with an MMP9 inhibitor or an MMP9 siRNA inhibited serum starvation-induced invasion.

Conclusion: Serum starvation could up-regulate MMP9 expression in NPC cells, contributing to NPC invasion. Therefore, serum starvation may promote malignancy of NPC cells but also support MMP9 as a potential therapeutic target to prevent NPC cell invasion and metastasis.

Keywords: Serum starvation; cell invasion; matrix metalloproteinase 9; nasopharyngeal carcinoma.