The Study Of Effect Erlotinib Combined With Radiotherapy

ObjectiveErlotinib is an epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI). It prohibits the proliferation, migration and the invasion of tumor cells by interrupting the multistage phosphorylation of EGFR signal channels, weakens adhesion and leads to cell apoptosis, and the clinical research showed its advantages in the treatments of therioma. As a molecular targeted drug, Erlotinib combined with radiotherapy can alleviate chemotherapy resistance and improve the curative effects of radiotherapy, which could be more promising therapeutic regimens in lung cancer treatments. In this study, the nude mice xenograft model of the human lung cancer cell A549 was established to explore the radio sensitizing effect of Erlotinib in lung adenocarcinoma radiotherapy treatment. MethodsTo establish the nude mice xenograft model of the human lung cancer cell A549 in vitro, the nude mice with tumo r growth were randomly divided into four groups : control group, radiotherapy group(X-ray), Erlotinib group and the combined group(erlotinib and radiotherapy). O nce every other day, the tumor major axis and short diameter were measured and the body weights of nude mice were recorded. The tumor volumes and the tumor growth inhibition rates were assayed to draw the growth curve of xenografted tumors. At the end of the treatments, xenografted tumors were removed and weighed, and tumor weight inhibitory rates were calculated. Blood was sampled from eyeball extirpating for blood routine test and blood biochemical test. Histopathological method was performed to examine the toxic effect of erlotinib on main tissues and organs. Immunohistochemistry are used to analyze Caspase3, Akt and p27 protein levels in tumor tissues after the combined treatments of erlotinib and radiotherapy.Results(1)The nude mice xenograft model of the human lung cancer cell A549 was established, and the peeled off tumors were visible to human eyes. The weights of tumor in Erlotinib+X-ray group were(0.82±0.11)g, which were lower than the Control group(1.35±0.15)g(P<0.01), and less than the X-ray group(1.02±0.13)g(P<0.01) and Erlotinib group(0.99±0.08)g(P<0.05).(2)The growth curve of xenografted tumors showed that the tumor volumes of the X-ray group and the Erlotinib group decreased over time compared with the control group. The tumor volumes in Erlotinib+X-ray group decreased more dramatically than the control group. The analysis of tumor growth inhibition rates and tumor weight inhibition rates demonstrated that the erlotinib combined with radiotherapy could effectively inhibit the tumor growth.(3)Blood was sampled from eyeball extirpating for blood routine test and blood biochemical test in the control group, X-ray group, Erlotinib group and Erlotinib+X-ray group.The results of blood biochemical test showed no significant difference in ALT, AST, BUN, CRE and LDH(P>0.05). The difference in blood routine indicators of four groups were not statistically significant(P>0.05).(4)The results of haematoxylin and eosin staining showed that there were no obvious pathological changes in main tissues and organs such as heart, liver, spleen, lung and kidney.(5) Immunohistochemistry showed that there are the increased protein expressions of p27 and Caspase3 in the X-ray group, comparing to the Control group and the Erlotinib group; The increased protein expression of p27 and Caspase3 in Erlotinib+ X-ray group compared with the X-ray group alone. The Akt expression was obvious in the Control group and the Erlotinib group, but decreased in the X-ray group, and obviously decrease of Akt protein level in the Erlotinib + X-ray group comparing to the X-ray group. The comparison between groups had significant statistical significance(P<0.05). ConclusionErlotinib as a molecular targeted agent, combined with radiotherapy, could effectively inhibit the growth of xenografted tumors and enhance the radiosensitizing effect of erlofinib on lung adenocarcinoma. Erlotinib combined with radiotherapy induced the expressions of apoptosis executor Caspase3 and tumor suppressor genes p27, inhibiting the expressions of anti-apoptotic genes of Akt. Erlotinib combined with radiotherapy was nearly no toxic to human body, which might be a safe and feasible treatments.