Inhibitory Effect And Mechanism Of Dendrobium Huoshanense On Non-small Cell Lung Cancer

As one of the most frequent types of cancer,lung cancer is a great threat to human health.The current treatments of lung cancer have many limitations and side effects,and are easy to induce drug resistance.The discovery of new anti-cancer drugs has always been the focus of research.Natural medicines can act on multiple targets with low side effects,so they have received wide attention.As a precious Chinese herbal medicine,Dendrobium huoshanense has extremely high medical value.This experiment explored the inhibitory effect and mechanism of Dendrobium huoshanense on non-small cell lung cancer(NSCLC)through two animal models and cell experiments.Lipid metabolism is essential for maintaining cellular homeostasis.And lipid metabolism can also promote tumor development by providing energy for tumor proliferation,invasion and metastasis.CD36,a fatty acid receptor,can regulate lipid metabolism and promote cancer progress,but there are few studies in the field of lung cancer.This study determined that CD36 could promote the proliferation and migration of NSCLC cells,and found that Dendrobium huoshanense inhibits CD36 expression,indicating that Dendrobium huoshanense inhibits lung cancer by regulating CD36.The main research contents and results are as follows:(1)In the urethane-induced primary lung cancer model,Dendrobium huoshanense significantly improved the survival rate of model mice,and inhibited lung cancer and inflammatory cell recruitment.In mechanism,Dendrobium huoshanense inhibited the expression of proliferating cell nuclear antigen(PCNA),Ki-67 and genes related to nuclear factor kappa-B(NF-kB)signaling pathway.(2)In the subcutaneous transplantation tumor model,Dendrobium huoshanense delayed the onset of solid tumors and reduced the tumor volume.In mechanism,Dendrobium huoshanense decreased the protein expression of PCNA,Ki-67 and Vimentin,and increased the m RNA levels of BAX and Cadherin 1(CDH1).(3)By analyzing the cancer database,we found that compared to lung cancer patients with low CD36 expression,patients with high CD36 expression had a lower overall survival rate.Through CD36 overexpression and knockdown cell models,we found that CD36 promoted cell proliferation and epithelial-mesenchymal transition(EMT)process,and had a positive regulatory effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR).(4)In both lung adenocarcinoma animal models and NCI-H520 lung squamous cell carcinoma cells,Dendrobium huoshanense decreases the protein and m RNA levels of CD36.In summary,we have demonstrated that Dendrobium huoshanense improves pulmonary inflammatory infiltration by inhibiting the NF-κB signaling pathway,and inhibits the proliferation of cancer cells as well as EMT process,thereby limiting the development of primary tumor and subcutaneous graft tumor,and raising the survival rate of model mice.In addition,we have clarified the CD36 can promote NSCLC,and Dendrobium huoshanense can inhibit CD36 expression,indicating that Dendrobium huoshanense may inhibit lipid metabolism through CD36,to limit the energy supply in tumor cells,consequently inhibiting the development of NSCLC.