Effect of receptor for hyaluronan-mediated motility inhibition on radiosensitivity of lung adenocarcinoma A549 cells

BACKGROUND: Receptor for hyaluronan-mediated motility (RHAMM), one of the major hyaluronic acid (HA) receptors, is upregulated in several forms of cancer and is a poor prognostic factor for non-small cell lung cancer (NSCLC) adenocarcinoma. RHAMM is also a potential therapeutic target for inhibition of tumor metastasis in NSCLC. However, its role in the radiosensitivity of NSCLC has yet to be determined. The aim of this study was to examine the inhibitory effect of RHAMM on the radiosensitivity of lung adenocarcinoma cell line A549 and its potential mechanism. METHODS: Expression of the RHAMM gene in NSCLC cell lines A549 and H460 was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Colony formation assays were used to analyze radiosensitivity of the two cell lines. Transfection with small interfering (si) RNA was used to inhibit expression of the RHAMM gene in the A549 cell line. A cell counting kit assay was used to analyze the cell proliferation rate; flow cytometry was used to evaluate the cell apoptosis and cell cycle; and Western blot was used to investigate the expression of phosphorylated-extracellular signal-regulated kinase 1/2 (p-ERK1/2) and ERK1/2 proteins. RESULTS: Expression of the RHAMM gene was negatively correlated with the radiosensitivity of NSCLC cell lines; inhibition of RHAMM gene expression enhanced the radiosensitivity of A549 cells. The mechanism for this inhibition was associated with reduced proliferation, increased apoptosis induced by radiotherapy, reduced ERK1/2 phosphorylation, and regulation of the ERK1/2 signaling pathway. Inhibition was not associated with increased G2/M phase arrest. CONCLUSIONS: RHAMM is a potential target for radiosensitization of lung adenocarcinomas.