缩氨基硫脲类化合物DpC抗头颈肿瘤活性的体外研究  

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

作　　者：陶泽璋[1] 喻迪[1] 王鹏举[1] 陈晨[1] 李芬[1] 

机构地区：[1]武汉大学人民医院耳鼻咽喉-头颈外科,武汉430060

出　　处：《肿瘤防治研究》2016年第2期106-111,共6页Cancer Research on Prevention and Treatment

摘　　要：目的比较缩氨基硫脲类化合物DpC与Dp44m T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Dp44m T对头颈部鳞状细胞癌Fa Du、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Dp44m T对Fa Du、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Dp44m T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Fa Du细胞3.93μmol/L与24.37μmol/L、Cal-27细胞2.79μmol/L与15.15μmol/L、SCC-9细胞15.61μmol/L与95.36μmol/L;DpC与Dp44m T均用浓度0、2.5、5、7.5μmol/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%;Fa Du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Dp44m T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Dp44m T,其中DpC的抗头颈肿瘤活性主要通过DNA损伤途径来实现。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 24.37gmol/L, 2.79 and 15.15pmol/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%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.

关 键 词：头颈肿瘤 DPC Dp44mT 抗肿瘤活性 

分 类 号：R914.5[医药卫生—药物化学]