Cao Hong-Ying, Ding Rui-Lin, Li Meng, Yang Mao-Nan, Yang Ling-Lin, Wu Jing-Bo, Yang Bo, Wang Jing, Luo Cui-Lian, Wen Qing-Lian
Department of Emergency, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China.
Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China.
Oncol Lett. 2017 Feb;13(2):605-612. doi: 10.3892/ol.2016.5508. Epub 2016 Dec 16.
The molecule 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid (danshensu), a herbal preparation used in traditional Chinese medicine, has been found to possess potential antitumor and anti-angiogenesis effects. The aim of the present study was to investigate the efficacy of the combination of radiation therapy (RT) with danshensu in the treatment of Lewis lung carcinoma (LLC) xenografts, whilst exploring and evaluating the mechanism involved. In total, 8-week old female C57BL/6J mice were randomly assigned into 3 groups to receive: RT, RT + cisplatin and RT + danshensu, respectively, when LLC reached 100-150 mm. Each group was divided into 7 subgroups according to the different irradiation doses that were administered. Tumor growth curves were created and the sensitization enhancement ratios of the drugs were calculated. The experiment was then repeated, and the 4 groups of tumor-bearing mice were treated with natural saline, danshensu, RT + danshensu and RT, respectively. The mice were sacrificed on day 7, and tumor tissue and blood were collected to determine microvessel density, the expression of proangiogenic factors, and the levels of blood thromboxane B and 6-keto-prostaglandin-F1α. Tumor hypoxia was also detected using fluorescence imaging. With respect to LLC xenografts, treatment with danshensu + RT significantly enhanced the effects of tumor growth inhibition (P<0.05). Furthermore, tumor vasculature was remodeled and microcirculation was improved, which significantly reduced tumor hypoxia (P<0.05). The present study demonstrated that danshensu significantly enhanced the radioresponse of LLC xenografts in mice. The mechanism involved may be associated with the alleviation of tumor cell hypoxia following treatment with danshensu + RT, caused by the improvement of tumor microcirculation and the remodeling of tumor vasculature.
分子3-(3,4-二羟基苯基)-2-羟基丙酸(丹参素)是一种用于传统中药的草药制剂,已被发现具有潜在的抗肿瘤和抗血管生成作用。本研究的目的是探讨放射治疗(RT)与丹参素联合治疗Lewis肺癌(LLC)异种移植瘤的疗效,同时探索和评估其相关机制。总共将8周龄雌性C57BL/6J小鼠随机分为3组,分别在LLC达到100 - 150 mm时接受:RT、RT + 顺铂和RT + 丹参素。根据给予的不同照射剂量,每组再分为7个亚组。绘制肿瘤生长曲线并计算药物的增敏增强比。然后重复该实验,将4组荷瘤小鼠分别用生理盐水、丹参素、RT + 丹参素和RT进行治疗。在第7天处死小鼠,收集肿瘤组织和血液以测定微血管密度、促血管生成因子的表达以及血中血栓素B和6-酮-前列腺素-F1α的水平。还使用荧光成像检测肿瘤缺氧情况。对于LLC异种移植瘤,丹参素 + RT治疗显著增强了肿瘤生长抑制效果(P<0.05)。此外,肿瘤血管系统得到重塑,微循环得到改善,显著降低了肿瘤缺氧(P<0.05)。本研究表明丹参素显著增强了小鼠LLC异种移植瘤的放射反应。其相关机制可能与丹参素 + RT治疗后肿瘤微循环改善和肿瘤血管系统重塑导致肿瘤细胞缺氧减轻有关。