The Expression And Clinical Significance Of P38MAPK In Human Lung Squamous Cell Carcinoma

Background:Lung cancer is the highest morbidity and mortality malignancy globally, whichseverely has threatened the health of humans. With the stage of China’s aging populationand industrialisation, environmental pollution and some negative lifestyle factors such assmoking have increased lung cancer mortality. Recently, morbidity crowd displaysyounger in average age trend also gradually. Lung cancer is divided into non-small celllung cancer (NSCLC) and small cell lung cancer (SCLC). Non-small cell lung cancer iscomposed of lung squamous cell carcinoma and adenocarcinoma of the lung. Lungsquamous cell carcinoma as the most common type of lung cancer, and it’s the maintreatment program is early surgery.But the patients with metastatic lung squamous cellcarcinoma are poor sensitivity to radiotherapy and chemotherapy. So it is a hot issue ofsocial concern that how to explore new drug target for clinical prevention and treatment. The occurrence and development of tumors are closely linked with intracellular signalingpathways beyond some genotype point mutations. The over-activation and block-out ofsignaling pathway in tumor cell affect self-regulation of cell, such as proliferation,differentiation, cell cycle and apoptosis, leading to cell proliferation and apoptosisimbalance, eventually to tumorigenesis.P38MAPKs, one of the important intracellular signaling pathways, play a significantrole in cell proliferation, differentiation, apoptosis, and inflammation. Disorderedproliferation is an major feature of the tumor. In recent years, It is found that p38MAPKsignaling pathway play an important part in tumor invasion and metastasis of themalignant cells. It is reported that p38MAPK may be associated with the cell cycle andapoptosis of lung adenocarcinoma, but its correlation with mechanisms of in pulmonarysquamous cell carcinoma is not clearly understood. The aim of this study was toinvestigate the relationship between P38MAPK expressions and the clinical pathologiccharacteristics of human lung squamous cell, and through the cell to study the possiblemechanism, and to further explore its potential mechanism in cells experiment.Objective:To investigate the P38MAPK expressions and its correlation with clinical pathologiccharacteristics of lung cancer, and to explore its mechanism of lung squamous cellcarcinoma by applying P38MAPK inhibitor SB203580.Method:(1) To investigate P38MAPK expression in LSCC,65patients were enrolled andtumor tissues were collected with matched non-tumor adjacent tissues (NAT). P38MAPKmRNA and protein levels were quantified with Real-time PCR, Western blots andimmunohistochemistry. Moreover, the distribution of P38and P-P38were furtherconfirmed by10paired of formalin-fixed paraffin-embedded LSCC and NAT byimmunohistochemistry. SPSS12.0was used to analyze the relationship between theP38MAPK expression and clinicopathological significance.(2) To determine the protein expression of P-P38in SK-MES-1by Western blotting;SK-MES-1cultured in vitro was treated with SB203580at concentrations of60,40,20,10, 5, and1μmo/L for24h, blank controls were also employed. The ratio of cell proliferationwas determined by MTT assay; Flow cytometry analysis was used to determine the cellcycle of SK-MES-1with SB203580at concentrations of20μmo/L and the negativecontrol without SB203580for24h.Result:(1) The P38MAPK expression did not differ between in tumor tissue and in controls atmRNA and protein levels（P＞0.05). However, P-P38was significantly expressed lower inLSCC compared to NAT;(2) The expression of P-P38was negatively correlated with the clinical stage and waspositively associated with histodifferentiation (P＜0.05);(3) P-P38was significantly expressed lower in SK-MES-1than BEAS-2B;(4) The SK-MES-1cells displayed a dose-dependent growth promoting in response toSB203580in MTT assays;(5) The percentage of SK-MES-1cells with10μM SB203580in S-phase wasdecreased and G2-phase was increased. The PI of SB203580was exceeded than thecontrol.Conclusion:The expression of P-P38in lung squamous cell carcinoma tissues and cells was lower.It was was negatively correlated with the clinical stage and was positively associated withhistodifferentiation. The inhibition mechanism was associated with inhibiting cellproliferation and proting cell cycle at G2/S phase.