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恩度注射液联合冷冻消融治疗肺腺癌A549移植瘤的实验研究

Experimental study of Endostar injection concomitant with cryoablation on lung adenocarcinoma A549 xenografts.

作者信息

Ma Chun-Hua, Jiang Rong, Li Jin-Duo, Wang Bin, Sun Li-Wei, Lv Yuan

机构信息

Department of Intervention, Tianjin Huanhu Hospital, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory, Tianjin, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2014 Jan;14(11):6697-701. doi: 10.7314/apjcp.2013.14.11.6697.

DOI:10.7314/apjcp.2013.14.11.6697
PMID:24377591
Abstract

OBJECTIVE

To explore the inhibiting effect and mechanism of Endostar injection concomitant with cryoablation on lung adenocarcinoma A549 xenografts in nude mice.

MATERIALS AND METHODS

A total of 24 nude mice with subcutaneous xenografts of the A549 cell line were established and divided into 4 groups when the maximal diameters of tumors became 1 cm: control group, Endostar group, cryoablation group and combination group (Endostar concomitant with cryoablation). The nude mice were sacrificed after 21-days treatment, tumour tissues were removed to measure their volume, in situ test of TdT-mediated dUTP nick end labeling (TUNEL) was adopted to determine the cellular apoptosis around freezing injury zones, and immunohistochemical SP test was applied for the detection of micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression levels.

RESULTS

At 21-days after treatment, the growth velocities of control group, Endostar group, cryoablation group and combination group were 236.7 ± 51.2%, 220.0 ± 30.6%, 159.5 ± 29.3% and 103.3 ± 25.5% (P<0.01), while cellular apoptosis rates of tumors were 21.7 ± 2.34%, (22.17 ± 1.47)%, 38.3 ± 1.37% and 49.2 ± 1.72%, (P<0.01), respectively, according to the immunohistochemical test. MVD and VEGF expression levels in the combination group were both lower than in other groups (P<0.01), also being positively related (r=0.925, P<0.01).

CONCLUSIONS

Endostar can significantly improve the inhibitory effects of cryoablation on xenografts of lung adenocarcinoma A549, and the mechanism is probably associated with its function as an inhibitor of tumour neo-angiogenesis through down-regulating VEGF expression.

摘要

目的

探讨恩度注射液联合冷冻消融对裸鼠肺腺癌A549移植瘤的抑制作用及机制。

材料与方法

建立24只皮下接种A549细胞系的裸鼠模型,待肿瘤最大直径达1 cm时分为4组:对照组、恩度组、冷冻消融组和联合组(恩度联合冷冻消融)。治疗21天后处死裸鼠,取出肿瘤组织测量体积,采用原位末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测冷冻损伤区周围细胞凋亡情况,应用免疫组织化学SP法检测微血管密度(MVD)及血管内皮生长因子(VEGF)表达水平。

结果

治疗21天后,对照组、恩度组、冷冻消融组和联合组肿瘤生长速度分别为236.7±51.2%、220.0±30.6%、159.5±29.3%和103.3±25.5%(P<0.01);免疫组化检测肿瘤细胞凋亡率分别为21.7±2.34%、(22.17±1.47)%、38.3±1.37%和49.2±1.72%(P<0.01)。联合组MVD及VEGF表达水平均低于其他组(P<0.01),且二者呈正相关(r=0.925,P<0.01)。

结论

恩度可显著增强冷冻消融对肺腺癌A549移植瘤的抑制作用,其机制可能与下调VEGF表达、抑制肿瘤新生血管生成有关。

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