Downregulation of P38 phosphorylation correlates with low-grade differentiation and proliferation of lung squamous cell carcinoma.

BACKGROUND: P38MAPK has been investigated as a tumor-related signaling molecule because of its apparent association with tumorigenesis. This study aimed to investigate P38MAPK expression and its role in lung squamous carcinoma (LSCC).

METHODS: The expression of P38MAPK and phosphorylated P38 (P-P38) in LSCC tissues and cells was examined by Western blot, real-time PCR, and immunohistochemistry. The influence of P38MAPK inhibitor SB203580 on the proliferation of LSCC cells was detected by MTT and flow cytometry.

RESULTS: The expression of P-P38 in LSCC tissues and cells was lower than that in cancer-adjacent normal tissues and normal bronchial epithelial cells (P<0.05). In addition, the expression of P-P38 was downregulated in LSCC tissues of poor differentiation, stages III and IV, and with lymph node metastasis compared with the LSCC tissues of well differentiation, stages I and II, and without lymph node metastasis (P<0.05). Moreover, the cell proliferation of LSCC SK-MES-1 cells treated by P38MAPK inhibitor SB203580 significantly increased in a concentration-dependent manner compared with that of SK-MES-1 cells without SB203580 (P<0.05). The inhibition of P38MAPK promoted the transition of the S phase to the G2 phase.

CONCLUSIONS: P-P38 was poorly expressed in LSCC tissues and cells. Its low expression was correlated with low-grade differentiation, lymph node metastasis, and advanced stage of LSCC. Inhibition of P38MAPK expression could significantly increase the proliferation of LSCC cells by promoting the transition of the S phase to the G2 phase.