期刊
TUMOR BIOLOGY
卷 35, 期 2, 页码 1169-1175出版社
SPRINGER
DOI: 10.1007/s13277-013-1156-6
关键词
Uveal melanoma; Bcl-2; Bax; Gemcitabine
类别
资金
- National Natural Science Foundation of China [81100683, 81372469, 81372909]
- Science and Technology Commission of Shanghai [13ZR1423600, 12ZR1417300]
- Shanghai PuJiang Program [13PJ1405700]
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.
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