Chun Eunyoung, Lee Ki-Young
Immune-2 Team, Mogam Biotechnology Institute, 341 Pojung-ri, Koosung-myun, Yongin-city, Kyonggi-do 449-910, Republic of Korea.
Biochem Biophys Res Commun. 2004 Mar 12;315(3):771-9. doi: 10.1016/j.bbrc.2004.01.118.
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 anti-apoptotic 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 Bcl 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.
在本研究中，我们调查了肝细胞癌（HCC）患者肿瘤对化疗药物紫杉醇产生耐药性的潜在机制。用紫杉醇治疗导致Hep3B肝癌细胞的生长受到有效抑制，但不影响从原发性HCC肿瘤建立的SNU - 368和SNU - 398细胞系的生长特性。紫杉醇诱导的生长抑制作用与细胞内p21水平相关，并导致细胞周期停滞在G2/M期。然而，紫杉醇治疗并未改变细胞内p53水平。相反，SNU - 398细胞表达高水平的抗凋亡蛋白Bcl - 2和Bcl - x(L)，并且在紫杉醇治疗后Bcl - x(L)水平可进一步诱导。相比之下，Hep3B细胞表达Bcl家族的促凋亡成员，并且在紫杉醇治疗后未能诱导Bcl - x(L)。因此，这些结果强烈表明Bcl - 2和Bcl - x(L)在介导对紫杉醇的耐药性中起重要作用。
