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缩氨基硫脲类化合物DpC抗头颈肿瘤活性的体外研究

陶泽璋, 喻迪, 王鹏举, 陈晨, 李芬

陶泽璋, 喻迪, 王鹏举, 陈晨, 李芬. 缩氨基硫脲类化合物DpC抗头颈肿瘤活性的体外研究[J]. 肿瘤防治研究, 2016, 43(2): 106-111. DOI: 10.3971/j.issn.1000-8578.2016.02.003
引用本文: 陶泽璋, 喻迪, 王鹏举, 陈晨, 李芬. 缩氨基硫脲类化合物DpC抗头颈肿瘤活性的体外研究[J]. 肿瘤防治研究, 2016, 43(2): 106-111. DOI: 10.3971/j.issn.1000-8578.2016.02.003
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TAO Zezhang, YU Di, WANG Pengju, CHEN Chen, LI Fen. In vitro Investigation of Antitumor Efficacy of DpC on Head and Neck Cancer[J]. Cancer Research on Prevention and Treatment, 2016, 43(2): 106-111. DOI: 10.3971/j.issn.1000-8578.2016.02.003
Citation: TAO Zezhang, YU Di, WANG Pengju, CHEN Chen, LI Fen. In vitro Investigation of Antitumor Efficacy of DpC on Head and Neck Cancer[J]. Cancer Research on Prevention and Treatment, 2016, 43(2): 106-111. DOI: 10.3971/j.issn.1000-8578.2016.02.003
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缩氨基硫脲类化合物DpC抗头颈肿瘤活性的体外研究

  • 430060 武汉，武汉大学人民医院耳鼻咽喉-头颈外科

详细信息
    作者简介:

    陶泽璋（1954-），男，博士，主任医师，主要从事耳鼻喉头颈外科学研究

    通讯作者:

    王鹏举，E-mail: wangpju@163.com

  • 中图分类号: R739.65

In vitro Investigation of Antitumor Efficacy of DpC on Head and Neck Cancer

  • Department of Otolaryngology, Head & Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China

摘要

    摘要
  • 摘要: 目的 比较缩氨基硫脲类化合物DpC与Dp44mT的体外抗头颈肿瘤（HNC）活性，并探讨DpC的作用机制。方法 采用CCK-8法测定DpC与Dp44mT对头颈部鳞状细胞癌FaDu、Cal-27、SCC-9等细胞系增殖能力的影响；应用流式细胞仪技术检测DpC与Dp44mT对FaDu、Cal-27、SCC-9细胞干预之后，细胞凋亡的变化。Western blot观察DpC对舌鳞癌细胞Cal-27的干预机制。 结果 DpC与Dp44mT对头颈肿瘤细胞有明显的抑制作用，其半数抑制率（IC50） 分别为FaDu细胞3.93 μmol/L与24.37 μmol/L、Cal-27细胞2.79 μmol/L与15.15 μmol/L、SCC-9细胞15.61 μmol/L与95.36 μmol/L；DpC与Dp44mT均用浓度0、2.5、5、7.5 μmol/L干预头颈肿瘤细胞后，随着作用浓度的增加，凋亡逐渐增加，其凋亡率分别为Cal-27细胞3.5%、15.8%、28.4%、39.8%与3.5%、18.3%、26.8%、26.1%，SCC-9细胞4.1%、10.7%、22.3%、28.9%与3.8%、7.2%、15.1%、22.4%；FaDu细胞4.2%、8.9%、17.1%、18.5%与4.2%、8.0%、14.4%、20.0%；在Cal-27细胞系中，DpC上调了DNA损伤相关通路蛋白，如p-ATM、p-Chk-1、p-ATR、p-Chk-2、P-Histone H2A.X、PARP、BRCA1、p-P53。 结论 DpC和Dp44mT均可抑制头颈肿瘤细胞的增殖和促进其凋亡，且DpC的抑制增殖和促进凋亡能力明显优于Dp44mT，其中DpC的抗头颈肿瘤活性主要通过DNA损伤途径来实现。

     

    Abstract: Objective To investigate the antitumor efficacy of DpC on head and neck cancer (HNC) cells compared with Dp44mT, and to further investigate the mechanism of DpC on tongue squamous carcinoma cells Cal-27. Methods CCK-8 assay was used to detect whether DpC could inhibit the proliferation of FaDu, Cal-27 and SCC-9 cells compared with Dp44mT; Annexin V-PI double staining was performed to detect the apoptosis proportion of FaDu, Cal-27 and SCC-9 cells treated with DpC and Dp44mT, then we used flow cytometry to detect the apoptosis; The mechanism of DpC on tongue squamous cell carcinoma cells Cal-27 was evaluated by Western blot. Results CCK-8 assay showed that DpC and Dp44mT significantly inhibited the proliferation of FaDu, Cal-27, SCC-9 cells in a concentration-dependent manner; the IC50 were 3.93 and 24.37μmol/L, 2.79 and 15.15μmol/L, 15.61 and 95.36μmol/L, respectively; flow cytometry showed that the proportion of apoptotic cells was gradually increased in a dose-dependent manner induced by DpC and Dp44mT (0, 2.5, 5, 7.5 μmol/L): and the apoptosis rates of HNC cells induced by DpC were significantly higher than those by Dp44mT: Cal-27 cells (Dp44mT：3.5%, 18.3%, 26.8%, 26.1%；DpC：3.5%, 15.8％, 28.4%, 39.8%)，SCC-9 cells (Dp44mT：3.8%, 7.2%, 15.1%, 22.4%；DpC：4.1%, 10.7%, 22.3%, 28.9%)，FaDu cells (Dp44mT：4.2%，8.0%，14.4%，20.0%；DpC：4.2%, 8.9%, 17.1%, 18.5%)；Western blot showed that the expression of DNA damage related proteins, such as p-ATM, p-Chk-1, p-ATR, p-Chk-2, P-Histone H2AX, PARP, BRCA1, p-P53, were up-regulated with increased DpC concentration in Cal-27 cells. Conclusion DpC and Dp44mT could inhibit the proliferation and promote the apoptosis of HNC cells, and DpC has better antitumor efficacy than Dp44mT. Furthermore, the process may be associated with DNA damage.

     

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出版历程
  • 收稿日期:  2015-09-07
  • 修回日期:  2015-12-23
  • 刊出日期:  2016-02-24

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