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重组人血管内皮抑制素对食管癌放疗的影响。

Effect of recombinant human endostatin onradiotherapy for esophagus cancer.

机构信息

Department of Thoracic Surgery, No. 153 Hospital of Liberation Army, Zhengzhou, China.

Department of Cardiothoracic Surgery, Xiangya Hospital Central-South University, Changsha, China.

出版信息

Asian Pac J Trop Med. 2016 Jan;9(1):86-90. doi: 10.1016/j.apjtm.2015.12.017. Epub 2015 Dec 19.

Abstract

OBJECTIVE

To investigate the effect of radiotherapy plus recombinant human endostatin (RH-endostatin) on esophageal cancer and its mechanism.

METHODS

A total of 50 nudemice were equally randomized into control group, radiotherapy group, and combined therapy group I, II, and III after inoculating with Eca109 cell suspension (1 × 10(7) cells/mL). On the day of grouping, control group and radiotherapy group were injected normal saline, while radiotherapy group and 3 combined therapy groups received radiotherapy; besides, combined therapy group I, II, and III was injected RH-endostatin of 2.5, 5, 10 mg/kg respectively. After 3-week therapy, the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined. In vitro, Eca109 cells were divided into control group, radiotherapy group, and combined therapy group. Forty-eight hours after treatment, cell cycle distribution and apoptosis rate were detected, and the activity of VEGF signal paths was semiquantitatively analyzed.

RESULTS

Since the 6th day of treatment, the relative tumor proliferation rate of combined therapy group II was lower than radiotherapy group (P < 0.05) and ≤40% since the 15th day. Average microvessel density and EGFR expression in combined therapy group II were lower than radiotherapy group (P < 0.05). In vitro, the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells, while the apoptosis rate and the expression of VEGF, AKT, p-AKT, ERK1/2 and p-ERK1/2 in combined group were higher than that in radiotherapy group (P < 0.05).

CONCLUSIONS

RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer, which may be partly realized by inhibiting the activity of VEGF related signal paths.

摘要

目的

探讨放疗联合重组人血管内皮抑制素(rh-endostatin)治疗食管癌的作用及其机制。

方法

接种 Eca109 细胞悬液(1×10(7)个/ml)后,将 50 只裸鼠等分为对照组、放疗组及联合治疗组 I、II、III。分组当天,对照组和放疗组注射生理盐水,放疗组和 3 个联合治疗组给予放疗;同时,联合治疗组 I、II、III 分别注射 2.5、5、10mg/kg rh-endostatin。治疗 3 周后,取各组肿瘤,检测肿瘤微血管密度和血管内皮生长因子(VEGF)表达。体外实验,将 Eca109 细胞分为对照组、放疗组和联合治疗组。治疗 48h 后,检测细胞周期分布和凋亡率,半定量分析 VEGF 信号通路活性。

结果

治疗第 6 天起,联合治疗组 II 的相对肿瘤增殖率低于放疗组(P<0.05),第 15 天起均≤40%。联合治疗组 II 的平均微血管密度和表皮生长因子受体(EGFR)表达均低于放疗组(P<0.05)。体外,联合治疗组细胞 S 期和 G2/M 期的细胞百分比低于放疗组,凋亡率及 VEGF、AKT、p-AKT、ERK1/2、p-ERK1/2 的表达均高于放疗组(P<0.05)。

结论

rh-endostatin 增强了放疗治疗食管癌的疗效,其机制可能部分是通过抑制 VEGF 相关信号通路的活性实现的。

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