Effects Of Different Delivery Methods Of Endostatin On Lung Adenocarcinoma And Human Umbilical Vein Endothelial Cells

BackgroundLung cancer is one of the major fatal malignancies with high morbidity and mortality. Despite significant improvements in recent therapeutic technologies, the incidence of lung cancer continues to rise in the globe. In recent decades, angiogenesis inhibitors have shown great potential in suppressing tumor growth and have thus become of interest in the research of cancer therapies due to its crucial role in the pathogenesis of tumors. Endostatin (endostar) is one of the potent anti-angiogenesis agents and has been used in clinical cancer treatment for years. However, it is still unclear how endostatin could play its maximum efficiency. This study is aimed to explore the optimal therapeutic regimen of endostatin by changing the concentration and frequency of the administration.ObjectiveTo explore the inhibitory effect of endostatin with different methods of administration on A549 cells, vascular endothelial cells and its effect on transplanted tumor in BALB/c nude mice.MethodsMTT was used to examine the cell proliferative rate of A549 cells and vascular endothelial cells under different concentration of endostatin. By comparing the masses of transplanted tumors formed in BALB/c nude mice, determined which method of administration was best to inhibit tumor formation. Immunohistochemical staining was applied to detect the expression of CD31 and CD34 in the masses formed at the injection sites in mice.Results1. Among those different concentrations, only 1μg/ml of endostatin had an inhibitory effect on the proliferation of A549 cells (P<0.05).2. Endostatin didn’t affect the proliferation of vascular endothelial cells (P>0.05).3. In vivo experiments, both administration of endostatin alone and the combination of endostatin and cisplatin can suppress the growth of tumors (P<0.05). In addition, the combinational therapy was more effective than the separate therapy.4. When endostatin was administered alone, the administration of every other day played the most effect in inhibiting the tumor volume by 50.74%. As to the combined regimens, the administration of endostatin (1 time/day) and cisplatin (1 time/week) showed the maximum inhibition rate (96.41%).5. The results of immunohistochemistry showed that, compared with the control group, the expression of CD31 and CD34 in the inoculated tumors formed in the mice that received therapy was downregulated (P<0.05).ConclusionAngiogenesis plays a key role in promoting growth of tumors. In the present study, the 1μg/ml of endostatin could inhibit the proliferation of A549 cells in vitro. But endostatin had no effect on the proliferation of vascular endothelial cells in vitro. In the in vivo study, the combination of endostatin and Cisplatin exhibited a higher inhibition rate than the administration of endostatin alone and it would be better to administrate endostatin every day.