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Background and purpose of the late 20th century, a major advance in the treatment of cancer is the chemotherapy drug development and clinical application. These drugs through damage to cellular DNA or inhibit the function of microtubules, thus preventing cell proliferation, leading to cell death and to play the role of anti-tumor. In pursuit of the most significant kill tumor cells, the dose of the chemotherapy drug commonly used to the body of the maximum tolerated dose (Maximum Tolerated Dose MTD). The MTD chemotherapy often cause serious side effects in the body recover from chemotherapy damage intermittent period, the tumor cells (including selective drug-resistant clones) as well as its support role of stromal cells can also be re-proliferation. Therefore, MTD chemotherapy not only cause serious side effects, reduce the quality of life of cancer patients, but also prone to drug resistance, treatment is also poor. In order to avoid the problems caused by MTD chemotherapy, researchers have started looking for a new way of administration, aims to improve the anti-tumor and / or anti-metastatic effect and at the same time reduce the toxicity. Tumor angiogenesis is essential for the maintenance of primary tumor growth, invasion and metastasis. Judah Folkman in 1971, the first targeted treatment strategies for tumor angiogenesis, after people instead began to turn to study the anti-angiogenic effect of the chemotherapy drugs. In fact, all types of chemotherapy drugs through injury dividing cell's DNA or disrupt its microtubules exert anti-tumor effect. Endothelial cell division occurs during neovascularization, which is also included in tumor angiogenesis, the same substantially in a stationary state compared to normal blood vessels, tumor vascular endothelial cells in a high state of growth, is more sensitive to the cytotoxic drug. The study found that certain cytotoxic drug to inhibit the process of angiogenesis, especially in the case of low-dose, high-frequency administration. MTD chemotherapy treatment associated with a longer interval (usually 2 to 3 weeks), compared to the mode of administration, the low-dose, high-frequency or continuous administration of the targeting of tumor vascular endothelial stronger, this type of chemotherapy is called \Metronomic chemotherapy to the tumor vasculature genotype stability, activation of endothelial cells as therapeutic targets, can reduce the incidence of drug resistance, and improve the therapeutic effect, but also because of its low dosage can reduce the side effects of chemotherapy. In addition, metronomic chemotherapy and other anti-angiogenic drugs in combination there is a synergistic effect. Studies have shown that many tumors, progression, and chronic inflammation is closely related. The inflammatory reaction is carried out in addition to anti-tumor response can be caused, more is to promote the proliferation of tumor angiogenesis and metastasis. The the inflammatory angiogenesis seems to be a central force in tumor growth and spread, to be confirmed this view can be achieved through the application of the traditional anti-inflammatory drugs inhibit angiogenesis. Inflammatory angiogenesis theory proposed new therapeutic targets to inhibit tumor angiogenesis, anti-inflammatory treatment. Currently, the reported rhythm chemotherapy and anti-inflammatory treatment abroad rare domestic yet to see reported. Bearing Lewis lung cancer in C57BL / 6 mice, the topic model to explore the commonly used chemotherapy drug docetaxel (docetaxel) metronomic chemotherapy and anti-inflammatory drug dexamethasone (dexamethasone) inhibit tumor angiogenesis, but relatively metronomic chemotherapy control its toxicity to tumor and anti-inflammatory treatment. C57BL / 6 mice bearing Lewis lung cancer model established, were randomly divided into the following four groups: ① docetaxel rhythm group. Intraperitoneal injection of docetaxel 5mg/kg, once every d; ② ground dexamethasone group. Intraperitoneal injection of dexamethasone 5mg/kg, once a d; ③ combination group. Intraperitoneal injection of docetaxel 5mg/kg, once every d dexamethasone5mg/kg once per d; ④ control group. Intraperitoneal injection of saline 0.2mL, d. Groups of 10 mice. Of these groups were inoculated-6d (subcutaneous tumor of about 100 to 200mm ~~ 3) from the start of dosing, sustained delivery of 8d. The mice were observed daily diet, activity and general condition of. After inoculation, the mice were sacrificed all broken neck 15d. The course of the experiment, continuous measurement of the murine tumor volume and weight, weight change curve tumor growth curve and mice, respectively, observed inhibitory effects and side effects of each group. Said after the mice were sacrificed and tumor weight, tumor microvessel density (MVD) was measured with immunohistochemical methods and hypoxia-inducible factor 1-a (HIF-a), the expression of the nuclear transcription factor-κB (NF-κB) and routine histological observation. Experimental data using a statistical software SPSS10.0 statistical treatment groups MVD compared using one-way ANOVA, pairwise comparisons using LSD test; groups HIF-1a, NF-κB expression compared using the Mann-Whitney nonparametric test two independent samples of Comparative Law, with a = 0.05 as the level of inspection. Results 1. Docetaxel rhythm group, dexamethasone group and the combined group of tumor growth curve is more gentle, steep growth curve than control tumors. 2. The the docetaxel rhythm group, dexamethasone group and the combined group of mice does not appear significant weight loss, weight to rise slowly in a steady state; gradual increase in body weight of mice of the control group, the growth rate is faster. The end of the experiment, Dorsey his race rhythm group, dexamethasone group, the combined group and the control group, the average tumor weight (2.85 ± 0.30) g, (2.80 ± 0.31) g, (2.46 ± 0.21) g, (4.25 ± 0.42) g. 3. Visual observation of specimens, the tumors in the control group pseudomembranous incomplete tumor tissue ruddy color, crisp light; docetaxel metronomic group, dexamethasone group, the combined group pseudomembranous complete tumor mass, tumor tissue pale color, quality and tough; microscope histology (HE staining), the control group showed gray red, rich in blood vessels, central necrosis; docetaxel rhythm group, dexamethasone group, the center of the joint group of tumor tissue and the edge of the common foci or necrosis Vascular significantly reduced. 4. Docetaxel rhythm group, dexamethasone group, the combined group and the control group MVD (15.89 ± 2.28), (15.90 ± 1.92), (12.44 ± 1.72) and (27.10 ± 2.06). Docetaxel rhythm group, dexamethasone group and the combined group of MVD significantly compared with the control group decreased, and the difference was statistically significant (P <0.05). 5. Docetaxel rhythm group, dexamethasone group and the combined group of HIF-1a expression in tumor tissue than in the control group was significantly decreased, and the difference was statistically significant (P <0.05). 6. The rhythm group docetaxel, dexamethasone group and the combined group of NF-κB expression in tumor tissue compared with the control group significantly decreased, and the difference was statistically significant (P <0.05). Conclusion 1. The docetaxel rhythm chemotherapy and dexamethasone could effectively inhibit the growth and angiogenesis of Lewis lung carcinoma. 2. Docetaxel metronomic chemotherapy in combination with dexamethasone synergistic inhibition of Lewis lung cancer growth and angiogenesis, its role better than monotherapy group. 3. Docetaxel rhythm chemotherapy and dexamethasone by inhibiting the expression of HIF-1a and NF-κB inhibition of Lewis lung cancer growth and angiogenesis.
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