The enhancement of tumor radioresponse by combined treatment with cepharanthine is accompanied by the inhibition of DNA damage repair and the induction of apoptosis in oral squamous cell carcinoma
The enhancement of tumor radioresponse by combined treatment with cepharanthine is accompanied by the inhibition of DNA damage repair and the induction of apoptosis in oral squamous cell carcinoma
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DOI：
10.3892/ijo.2012.1501
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发表时间：
2012-08-01
影响因子：
5.2
通讯作者：
Ueyama, Yoshiya
中科院分区：
文献类型：
--
作者：
Harada, Toyoko;Harada, Koji;Ueyama, Yoshiya
在本研究中，我们研究了用千金藤碱（一种从千金藤中提取的双月桂碱生物碱）治疗是否可以改善口腔鳞状细胞癌 (OSCC) 细胞系 HSC2、HSC3 和 HSC4 对放射治疗的反应。我们研究了可能有助于千金藤素诱导的增强辐射反应的潜在机制。在体外用辐射或千金藤素观察到生长抑制。当用千金藤素处理癌细胞并随后进行放射治疗时，获得了协同抗增殖作用。 Cepharanthine 还通过辐射促进 3 种细胞系的有丝分裂死亡。培养的 OSCC 细胞 DNA 损伤修复分析结果表明，千金藤素对辐射后 DNA 双链断裂 (DSB) 修复具有很强的抑制作用。流式细胞仪显示，千金藤碱和放射线的联合治疗导致亚 G1 峰增加，并通过激活 caspase-3 显着诱导细胞凋亡。肿瘤异种移植研究表明，千金藤碱和放射线的结合可导致无胸腺小鼠 OSCC 肿瘤的生长抑制和肿瘤消退； HSC2 细胞中的肿瘤体积从 765.7 减少至 226.3 mm(3) (p
In the present study, we investigated whether treatment with cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepharantha improves the response to radiotherapy in the oral squamous cell carcinoma (OSCC) cell lines, HSC2, HSC3 and HSC4. We examined the potential mechanisms that may contribute to the enhanced radiation response induced by cepharanthine. Growth inhibition was observed in vitro with radiation or cepharanthine. A co-operative antiproliferative effect was obtained when cancer cells were treated with cepharanthine followed by radiation. Cepharanthine also promoted the mitotic death of 3 cell lines by radiation. The results from DNA damage repair analysis in the cultured OSCC cells demonstrated that cepharanthine had a strong inhibitory effect on DNA double-strand break (DSB) repair after radiation. The combined treatment of cepharanthine and radiation led to an increase in the sub-G1 peak as shown by flow cytometry, and markedly induced apoptosis through the activation of caspase-3. Tumor xenograft studies demonstrated that the combination of cepharanthine and radiation caused growth inhibition and tumor regression of OSCC tumors in athymic mice; tumor volume was reduced from 765.7 to 226.3 mm(3) in HSC2 cells (p