Effect of sinomenine hydrochloride on radiosensitivity of esophageal squamous cell carcinoma cells.
Effect of sinomenine hydrochloride on radiosensitivity of esophageal squamous cell carcinoma cells.
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盐酸青藤碱对食管鳞癌细胞放射敏感性的影响
DOI：
10.3892/or.2018.6228
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发表时间：
2018-04
期刊：
影响因子：
4.2
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Fu S;Jin L;Gong T;Pan S;Zheng S;Zhang X;Yang T;Sun Y;Wang Y;Guo J;Hui B;Zhang X
放射治疗是不能切除的局部晚期食管鳞状细胞癌(ESCC)的重要治疗手段之一，然而放射治疗的反应有时会受到放射抵抗发展的限制。盐酸青藤碱(SH)具有抗癌活性，但其对食管癌放射增敏的影响尚不清楚。我们测定了SH对ESCC细胞放射增敏的影响，并在体内外阐明了其潜在的放射增敏机制。用SH和辐射单独或联合作用于ESCC细胞。未处理的细胞作为对照。CCK-8法检测细胞增殖，克隆形成法检测放射增敏作用。流式细胞仪检测细胞周期时相和细胞凋亡。免疫印迹法检测bcl2、bax、细胞周期蛋白B1、CDK1、Ku86、Ku70、RAD51的表达。在体内，用BALB/c裸鼠建立了肿瘤移植瘤。采用免疫组织化学方法检测肿瘤组织中Ki-67和Bax的表达。SH通过诱导癌细胞发生G2/M期阻滞，抑制其生长，并显著提高其放射敏感性。SH联合放射治疗可明显增加ESCC细胞的凋亡率。SH增强ESCC细胞放射敏感性的分子机制与下调Bcl2、Cyclin B1、CDK1、Ku86、Ku70、RAD51和上调Bax蛋白表达有关。SH联合放射治疗明显延缓了体内移植瘤的生长。免疫组织化学分析显示，SH联合放疗组Bax的表达明显高于对照组，Ki-67的表达明显低于对照组。综上所述，我们的研究结果表明，SH可能通过诱导G2/M期阻滞、促进辐射诱导的细胞凋亡和抑制DSB修复途径来提高ESCC细胞对辐射的敏感性。SH有望成为提高食管癌放射治疗疗效的一种有前景的放射增敏剂。
Radiation therapy is one of the most important treatments for unresectable and locally advanced esophageal squamous cell carcinoma (ESCC), however, the response to radiotherapy is sometimes limited by the development of radioresistance. Sinomenine hydrochloride (SH) has anticancer activity, but its effect on the radiosensitivity of ESCC is unclear. We determined the effect of SH on the radiosensitivity of ESCC cells and elucidated its potential radiosensitization mechanisms in vitro and in vivo. ESCC cells were subjected to SH and radiation, both separately and in combination. Untreated cells served as controls. The CCK-8 assay was used to evaluate cell proliferation, and the clonogenic assay to estimate radiosensitization. Flow cytometry was used to investigate cell cycle phases and cell apoptosis. Bcl-2, Bax, cyclin B1, CDK1, Ku86, Ku70, and Rad51 expression was evaluated using western blotting. In vivo, tumor xenografts were created using BALB/c nude mice. Tumor-growth inhibition was recorded, and Ki-67 and Bax expression in the tumor tissues was assessed using immunohistochemistry. SH inhibited ESCC cell growth and markedly increased their radiosensitivity by inducing G2/M phase arrest. SH combined with radiation therapy significantly increased ESCC cell apoptosis. The molecular mechanism by which SH enhanced radiosensitivity of ESCC cells was related to Bcl-2, cyclin B1, CDK1, Ku86, Ku70, and Rad51 downregulation and Bax protein expression upregulation. SH combined with radiation considerably delayed the growth of tumor xenografts in vivo. Immunohistochemical analysis showed that in the SH combined with radiation group, the expression of Bax was significantly higher while that of Ki-67 was lower than the expressions in the control groups. Taken together, our findings showed that SH could improve the sensitivity of radiation in ESCC cells by inducing G2/M phase arrest, promoting radiation-induced apoptosis and inhibiting DSB-repair pathways. SH appears to be a prospective radiosensitizer for improving the efficacy of radiotherapy for ESCC.
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4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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