Wang Jing, Jia Renbing, Zhang Yidan, Xu Xiaofang, Song Xin, Zhou Yixiong, Zhang He, Ge Shengfang, Fan Xianqun
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China.
Tumour Biol. 2014 Feb;35(2):1169-75. doi: 10.1007/s13277-013-1156-6. Epub 2013 Sep 7.
Gemcitabine (GEM), a new cytotoxic agent, was shown to be effective against uveal melanoma (UM) which is noted for its resistance to chemotherapy. In this study, we found the different sensitivities to GEM in UM cell lines and identified apoptotic cell death as the cause of GEM cytotoxicity. Both UM cell lines showed an increase in Bax protein levels and activation of cleaved Caspase 3. Additionally, SP6.5 cells showed a gradual increase in Bcl-2 expression over time, whereas VUP cells showed almost none. After interfering in the expression of Bcl-2, the sensitivity to GEM was obviously enhanced in SP6.5 cells. These results suggest that an increase in Bax plays a crucial role in apoptotic cell death induced by GEM in the absence of p53. Moreover, inhibition of Bcl-2 expression can efficiently enhance the cytotoxic effect of, and sensitivity to, GEM in UM cells.
吉西他滨（GEM）是一种新型细胞毒性药物，已被证明对化疗耐药的葡萄膜黑色素瘤（UM）有效。在本研究中，我们发现UM细胞系对GEM的敏感性不同，并确定凋亡性细胞死亡是GEM细胞毒性的原因。两种UM细胞系均显示Bax蛋白水平升高和裂解的半胱天冬酶3激活。此外，SP6.5细胞中Bcl-2表达随时间逐渐增加，而VUP细胞几乎没有。干扰Bcl-2表达后，SP6.5细胞对GEM的敏感性明显增强。这些结果表明，在缺乏p53的情况下，Bax的增加在GEM诱导的凋亡性细胞死亡中起关键作用。此外，抑制Bcl-2表达可有效增强GEM对UM细胞的细胞毒性作用和敏感性。
