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黄芪多糖联合顺铂降低Lewis肺癌荷瘤小鼠血清中CD44、Ⅳ型胶原和透明质酸水平

[Astragalus polysaccharides combined with cisplatin decreases the serum levels of CD44 and collagen type IV and hyaluronic acid in mice bearing Lewis lung cancer].

作者信息

Ming Haixia, Chen Yanwen, Zhang Fan, Wang Qiang, Dong Xiaoli, Gu Jing, Li Yang

机构信息

Department of Physiology, Gansu Key Laboratory of Chinese Medicine Pharmacology and Toxicology, Gansu College of Traditional Chinese Medicine, Lanzhou 730000, China.

Department of Anatomy, Gansu Key Laboratory of Chinese Medicine Pharmacology and Toxicology, Gansu College of Traditional Chinese Medicine, Lanzhou 730000, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 Jul;31(7):909-13.

Abstract

OBJECTIVE

To observe the effects of Astragalus polysaccharides (APS) combined with cisplatin on growth of Lewis lung cancer (LLC), serum content of collagen type IV (Col4) and hyaluronic acid (HA), and CD44 protein level in LLC-bearing mice.

METHODS

C57BL/6J mice (n=90) were randomly divided into 2 groups, 10 mice for blank control group, and 80 mice for tumor-bearing group. The tumor-bearing group was then randomized into 8 subgroups, 10 mice for each subgroup. The tumor-bearing mice were treated by peritoneal injection of normal saline, 6 mg/kg cisplatin, 50, 100, 200 mg/kg APS, and 3 mg/kg cisplatin combined with 50, 100, 200 mg/kg APS, respectively. APS (0.3 mL) was injected once a day from the first to the 20th day after LLC transplantation, and cisplatin of the same volume was injected once a week. On the 21st day, the blood was taken from the eyeballs of all experimental mice. Col4 and HA contents in serum were detected by radioimmunoassay. The expression of CD44 in transplanted tumor cells was determined by immunohistochemistry and image analysis. The inhibition rate of tumor growth was also counted.

RESULTS

The inhibition rates of 6 mg/kg cisplatin, 50, 100, 200 mg/kg APS, and 3 mg/kg cisplatin combined with 50, 100, 200 mg/kg APS on LLC growth in the mice were 49.30%, 17.21%, 39.68%, 42.98%, 51.02%, 57.21% and 65.11%, respectively. Compared with the control subgroup of the tumor-bearing group, cisplatin, APS and cisplatin combined with APS reduced significantly the Col4 and HA content in serum, and down-regulated the expression of CD44.

CONCLUSION

APS can inhibit the growth of LLC cells, reduce the Col4 and HA content in serum, down-regulate the expression of CD44 protein in LLC-bearing mice, and enhance the therapeutic effect when combined with cisplatin, indicating that it can decrease the toxicity of cisplatin against tumor.

摘要

目的

观察黄芪多糖(APS)联合顺铂对Lewis肺癌(LLC)小鼠肿瘤生长、血清Ⅳ型胶原(Col4)和透明质酸(HA)含量以及LLC小鼠CD44蛋白水平的影响。

方法

将90只C57BL/6J小鼠随机分为2组,空白对照组10只,荷瘤组80只。荷瘤组再随机分为8个亚组,每组10只。分别对荷瘤小鼠腹腔注射生理盐水、6 mg/kg顺铂、50、100、200 mg/kg APS以及3 mg/kg顺铂联合50、100、200 mg/kg APS。自LLC移植后第1天至第20天,每天注射一次APS(0.3 mL),每周注射一次相同体积的顺铂。第21天,采集所有实验小鼠的眼球血。采用放射免疫法检测血清中Col4和HA含量。通过免疫组织化学和图像分析测定移植瘤细胞中CD44的表达。同时计算肿瘤生长抑制率。

结果

6 mg/kg顺铂、50、100、200 mg/kg APS以及二者联合组对小鼠LLC生长的抑制率分别为49.30%、17.21%、39.68%、42.98%、51.02%、57.21%和65.11%。与荷瘤组的对照亚组相比,顺铂、APS以及二者联合用药均显著降低了血清中Col4和HA的含量,并下调了CD44的表达。

结论

APS可抑制LLC细胞生长,降低血清中Col4和HA含量,下调LLC小鼠CD44蛋白表达,与顺铂联合应用可增强治疗效果,提示其可降低顺铂的肿瘤毒性。

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