Oridonin Contributes To Enhancing Radiosensitivity Of Non-small Cell Lung Cancer Cells By Promoting Cell Apoptosis

Background:Surgical resection is the most effective way to treat lung cancer.However,most patients with lung cancer,especially 80% of non-small cell lung cancer(NSCLC),have no obvious symptoms early.Most patientscan not accept radical surgery when diagnosed,only through chemotherapy or local radiotherapy to delay tumor progress.Thus the comprehensive treatment of radiotherapy and chemotherapy is the main treatment for patients with advanced lung cancer.However,drug and radiotherapy resistance has been two major problems faced by clinicians,and the related research on radiation resistance is still few.Recently,research on radiotherapy sensitizers has become a research focus,but there is little research on the clinical effects of traditional Chinese medicine as radiosensitizers.Wintergrass,also known as oridonin,is an active ingredient of tetracyclic diterpene isolated from Rabdosia rubescens(Hemsl)Hara from the Labiatae family,which is widely recognized as Chinese herbal medicine against cancer.However,it is rarely reported whether oridonin can improve the radiosensitivity of tumor cells.In this study,we study the function and mechanism of oridonin on the radiotherapy sensitivity of lung cancer cells,which provides a new way for the improvement of the radiosensitivity of lung cancer.Methods:The cell viability of lung cancer cells was studied by MTT assay.The cell proliferation ability of lung cancer cells was studied by clonal formation experiment.Western blot was used to study the molecular mechanism of the effect of oridonin on the radiosensitivity of lung cancer cells.Statistical analysis including independentsample T test and variance analysis were performed to analyze the experiment results.Results:First of all,we have demonstrated that Oridonin can inhibit proliferation and promote the apoptosis of lung cancer cells in a time-and dose-dependent manner.At the same time,we demonstrated that radiation therapy significantly increases lung cancer cell apoptosis and reduces its proliferation.To investigate whether oridonin improves the radiosensitivity of lung cancer cells,we compared the radiotherapy sensitivity of lung cancer cells which pretreated with oridonin or not.Oridonin is shown to greatly improve the radiotherapy sensitivity of lung cancer cells.As cell apoptosis plays an important role in radiotherapy,we hypothesize whether the enhanced effect of oridonin on radiotherapy sensitivity of lung cancer cells is by increasing cell apoptosis.We then detected the expression of apoptosis protein in the lung cancer cells pretreated with oridonin,and found that Oridonin significantly increases the expression of apoptosis-related protein BAX,but decreases the expression of apoptosis inhibitor BCL-2.Thus we confirmed that the promoted effect of oridonin the radiotherapy sensitivityof lung cancer cell may be through regulating BAX / BCL-2-related apoptosis pathway.Conclusion:Oridonin can not only inhibit the proliferation of lung cancer cells and promote the apoptosis of lung cancer cells,but also enhance the sensitivity of lung cancer cells to radiotherapy,which reduces the incidence of radiotherapy tolerance.Oridonin can promote the radiosensitivity of lung cancer cells by up-regulating apoptosis-related protein BAX expression and down-regulatingthe expression of apoptosis inhibitor BCL-2.