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

Biochem Biophys Res Commun. 2004 Mar 12;315(3):771-9. doi: 10.1016/j.bbrc.2004.01.118.

Abstract

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.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • G2 Phase / drug effects
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism*
  • Mice
  • Mice, Nude
  • Paclitaxel / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation
  • Xenograft Model Antitumor Assays
  • bcl-X Protein

Substances

  • Antineoplastic Agents, Phytogenic
  • BCL2L1 protein, human
  • Bcl2l1 protein, mouse
  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-X Protein
  • Paclitaxel