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Pattern of apoptosis by NS398, a selective COX-2 inhibitor, in hepatocellular carcinoma cell lines

Mi Kyung Park1, Moon Kyu Kim, Jung Chul Kim

  • 1Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.

Cancer Research and Treatment
|December 4, 2009
PubMed
Abstract

Insights

The cytotoxic effect of NS398 on hepatocellular carcinoma cells was independent of COX-2 expression and did not involve caspases. Further research is needed to evaluate COX-2 inhibitors for cancer prevention.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Hepatocellular carcinoma (HCC) is a significant global health concern.
  • Selective cyclooxygenase-2 (COX-2) inhibitors, like NS398, have shown potential in inhibiting the growth of COX-2 expressing HCC cells.

Purpose of the Study:

  • To investigate if the cytotoxic effect of NS398 is dependent on COX-2 expression in HCC cells.
  • To determine the involvement of caspases in NS398-induced apoptosis in HCC cells.

Main Methods:

  • RT-PCR and Western blot were used to assess COX-2 expression in SNU 423 and SNU 449 HCC cell lines.
  • MTT assays measured cytotoxicity in the presence or absence of caspase inhibitors.
  • Flow cytometry and a Cell Death ELISA kit analyzed cell cycle distribution and apoptosis.

Main Results:

  • COX-2 expression was detected in SNU 423 cells but not in SNU 449 cells.
  • NS398 induced dose- and time-dependent growth inhibition and apoptosis in both cell lines.
  • Caspase inhibitors (z-VAD-fmk and Ac-DMQD-CHO) did not attenuate the cytotoxic effect of NS398.

Conclusions:

  • The cytotoxic effects of NS398 on HCC cells are independent of COX-2 expression.
  • Caspases are not involved in NS398-induced apoptosis in these HCC cell lines.
  • The utility of COX-2 inhibitors for HCC prevention requires careful evaluation.
Keywords:
ApoptosisCyclooxygenase 2Hepatocellular carcinomaNS398

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