Nitidine Chloride Suppresses NEDD4 Expression In Non-small Cell Lung Cancer

Background:Globally,lung cancer is one of the malignant tumors with the fastest increase in morbidity and mortality.About 1.2 million people die of lung cancer every year in the world,among which 80%-85% of lung cancer patients are non-small cell lung cancer(NSCLC),which is difficult to diagnose in early stage and is mainly dominated by radiotherapy and chemotherapy.Nitidine chloride(NC),a component extracted from the root of zanthoxylum ruticaceae,has been shown to inhibit the proliferation of tumor cells in a variety of tumors,but has not been reported in non-small cell lung cancer.Neuronally expressed developmentally downregulated 4(NEDD4)belongs to HECT-type E3 ubiquitin-ligase,and relevant reports have shown that abnormal regulation of NEDD4 protein is related to the occurrence and development of cancer,and plays an oncogene role in non-small cell lung cancer.However,the mechanism of whether nitidine chloride inhibits lung cancer by affecting the expression of NEDD4 has not yet been clarified.Therefore,this paper will further explore the role of diamidine chloride in lung cancer cells and whether it partially inhibits the growth and metastasis of lung cancer cells through NEDD4.Objective:To investigate the effect of nitidine chloride in the treatment of non-small cell lung cancer(NSCLC)and to verify its effect on the expression of NEDD4.To investigate the effects of nitidine chloride on the proliferation,invasion and apoptosis of lung cancer cells,and to provide potential therapeutic drugs and novel molecular targeting markers for clinical treatment of patients with non-small cell lung cancer.METHODS:Using human lung cancer cell lines NCI-H1299 and H460 as research objects,the effect and mechanism of nitidine chloride in lung cancer were studied by RT-PCR,Western Blotting,flow cytometry and MTT assay.TCGA database,wound healing experiment and transwell chamber migration and invasion assays dissected that NC exposures resulted in attenuation of cell migratory and invasiveness activity in H1299 and H460 cells.NEDD4 small interfering RNA and NEDD4 c DNA were constructed and transfected into lung cancer cells to reduce and increase the expression of NEDD4 in cells,and the combined action of nitidine chloride on cells was conducted to verify whether nitidine chloride could inhibit lung cancer cells by partially affecting the expression of NEDD4.Results:We found that nitidine chloride can suppress cell migratory and invasiveness activity and induce cell apoptosis in vitro,and exert its anticancer activity Through the literature and reports found NEDD4 in non-small cell lung cancer with high expression,showing the role of oncogene,at the same time and analyze the cancer genome atlas(TCGA)database,high expression NEDD4 surial for patients with NSCLC is inversely proportional to,and the expression of tumor tissue is higher than normal lung tissue adjacent to carcinoma,consistent with the literature reported,determine the target genes of NEDD4 for lung cancer,and may be partially involved in the two needle alkali chloride mediated antitumor activity.The high expression of NEDD4 in lung cancer cells can reverse the effect of nitidine chloride on cell proliferation,neutralize the effect of nitidine chloride on cell migration and metastasis and induce apoptosis.When the expression of NEDD4 is down-regulated,it can promote the anti-tumor activity of nitidine chloride,enhance the inhibition ability of migration and invasion of lung cancer cells,and further promote cell apoptosis.Conclusion: In vitro,nitidine chloride can inhibit the proliferation of lung cancer cells,inhibit cell migration,invasion,and metastasis,and induce cell apoptosis.The expression of NEDD4 in lung cancer was down-regulated by nitidine chloride.The high expression of NEDD4 reversed the inhibitory effect of nitidine chloride on lung cancer cells,and down-regulation of NEDD4 could promote the antitumor activity of nitidine chloride.Nitidine chloride may have anticancer activity in lung cancer partly by down-regulating the expression of NEDD4.