Bcl-2 and Bcl-xL are important for the induction of paclitaxel resistance in human hepatocellular carcinoma cells

被引:90
作者
Chun, EY
Lee, KY
机构
[1] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA
[2] Mogam Biotechnol Inst, Immune 2 Team, Yongin 449910, Kyonggi, South Korea
关键词
D O I
10.1016/j.bbrc.2004.01.118
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this study we have investigated the mechanism underlying resistance to the chemotherapeutic drug paclitaxel in tumors of hepatocellular carcinoma (HCC) patients. Treatment with paclitaxel led to potent inhibition of growth of Hep3B hepatoma cells, but did not affect the growth properties of SNU-368 and SNU-398 cell lines that were established from primary HCC tumors. The growth inhibitory effect induced by paclitaxel correlated with levels of intracellular p21 and resulted in cell cycle arrest at the G2/M phase. However, paclitaxel treatment did not alter intracellular p53 levels. Instead, SNU-398 cells express high levels of the antiapoptotic Bcl-2 and Bcl-x(L) proteins and the level of Bcl-x(L) could be further induced upon paclitaxel treatment. In contrast, Hep3B cells express pro-apoptotic members of the Bel family and fail to induce Bcl-x(L) upon paclitaxel treatment. Therefore, these results strongly suggest that Bcl-2 and Bcl-x(L) play an important role in mediating resistance to paclitaxel. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:771 / 779
页数:9
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