Wogonin Blocks Proliferation And Induces Apoptosis Of Lung Squamous Carcinoma QG56Cells Through Downregulation Of P-ERK1/2

Objective: Lung cancer is the most morbidity and mortality of malignanttumors,non-small-cell lung cancer (NSCLC) accounts for approximately85%of alllung cancer patients. More than50%of all patients with NSCLC already have locallyadvanced or metastatic disease at the time of diagnosis.The treatment of NSCLC israpidly evolving due to the introduction of new cytotoxic regimens and the developmentof specific biological cancer therapies. However, despite the many therapeutic optionsthat have been introduced over the last several years, the median5-year survival rate forpatients with lung cancer is still only approximately15%. Therefore, to enhance thesurvival rate of the patients with new methods needs to be solved urgently. In order todecrease cancer mortality we should focused on health initiatives including prevention,early detection, and effective treatments. A growing amount of research suggests thatnumerous naturally occurring compounds act as antioxidants, cancer preventative andtherapeutic agents. Plant chemical drugs can treat some human cancers, in clinicaltreatment of cancer patients, many prescription drug are derived from natural plantspecies. Wogonin is labium plants of the main active constituents of radix scutellariae,which belongs to phenolic antioxidants, and it’s one of flavonoids compounds, withstrong anti-inflammatory, antioxidant activity, the study found that in recent years,wogonin has obvious antitumor function. We want to investigate the effect of wogoninon the proliferation and apoptosis of lung squamous carcinoma QG56cells, and toexplore its effection on regulation of p-ERK1/2.Methods: MTT assay and flow cytometry were used to detest the growthinhibition and apoptosis of QG56cells induced by different concentration ofwogonin.Cell morphological change was observed by microscope. Observe the cellcycle change under the Fluorescence microscope, protein level of p-ERK1/2was revealed by western blot analysis.Results: The results indicated that wogonin could inhibit the proliferation of theQG56cells significantly and promote apoptosis in a time and dose dependent manner。The results of MTT indicate that different concentration of wogonin can inhibit theproliferation of QG56cells respectively. With12.5μM wogonin treated for24hours,the inhibit rate of lung cancer cells QG56is about17.27%, and the inhibit rate of160μM is approximate40.55%after treated24hours. After3tests treated with25、50、100and160μmol/L wogonin for24hours, the average inhibit rate are（20.51±1.32）%、（29.55±1.02）%、（32.56±0.51）%and（40.18±0.37）%respectively. After treatmentwith wogonin for24h、48h、72h, the IC50value were (63.45±7.02)μmol/L、(52.60±8.09)μmol/L and (38.37±7.82)μmol/L respectively. Further confirmed by flowcytometry, when25μmol/L、50μmol/L、100μmol/L and160μmol/L of wogonin weregiven to the QG56cells for48h,the apoptosis rates were20.79%、37.28%、50.88%and65.56%respectively. The highest apoptosis rate is65.62%when the concentration ofwogonin was up to160μmol/L.Cell morphological change was observed by microscope.In the control group, the cells with round caryon were polygon, thin and flat, and theywere fast clingy, In the wogonin treated groups, with the increase of drugconcentration,the cells show a typical morphological changes of apoptosis, the cellsbecame contracted and poor at clingy, disappear of ecphyma of the cells, and chromatincondensation. The results of Flow cytometry indicates that，cell apoptosis rate increaseswith the increase of wogonin concentration, which demonstrate that wogonin caninduce QG56cells apoptosis obviously. To observe the morphology of cells apoptosisunder the fluorescence microscope,we found early apoptosis are green fluorescent butthe late are red. Western blot detects the expression of phosphorylation extracellularsignal regulating kinase（p-ERK1/2）protein are downregulated in QG56cells treatedwith wogonin in a concentration dependent manner, which demonstrates that wogonininduces lung cancer cells QG56apoptosis and RAF-MAPK-ERK signal pathway maybethe key way.Conclusion:1) With the increasing of the concentration of wogonin, QG56cell growthinhibition rate increased significantly, which indicates that wogonin can inhibits lungcancer cell QG56growth on the role of proliferation.2) With the increasing of the concentration of wogonin, QG56cell apoptosis rateincreased significantly, which indicates that wogonin can induce lung cancer cell QG56 to apoptosis.3) With the increasing of the concentration of wogonin, the expression ofp-ERK1/2decreased, which suggests that the mechanisms of action maybe related toinhibite p-ERK1/2for key molecular signaling pathways, wogonin known as hope forthe new cancer drugs for clinical application.