Blocking of PI3K/Akt pathway enhances apoptosis induced by SN-38, an active form of CPT-11, in human hepatoma cells

  • Authors:
    • Naoki Koizumi
    • Etsuro Hatano
    • Takashi Nitta
    • Masaharu Tada
    • Nobuko Harada
    • Kojiro Taura
    • Iwao Ikai
    • Yasuyuki Shimahara
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/ijo.26.5.1301
  • Pages: 1301-1306
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Abstract

Hepatocellular carcinoma (HCC) is a common malignancy and often resistant to chemotherapy. Many chemotherapy regimens have been tried to control advanced HCC, but have produced a low response rate and no clear impact. CPT-11, a derivative of camptothecin, works as type-I DNA topoisomerase inhibitor and showed a major objective response rate in patients with metastatic colorectal cancer. In this study, the mechanism underlying chemo-resistance to SN-38, an active form of CPT-11, in HCC was investigated in relation to anti-apoptotic pathways NF-κB and PI3K/Akt. Hep3B was the most resistant to SN-38 among three hepatoma cell lines. NF-κB was constitutively activated in Hep3B, and SN-38 further enhanced the nuclear translocation of NF-κB. However, inactivation of NF-κB by adenovirus expressing IκB super-repressor or MG-132, proteasome inhibitor, did not sensitize Hep3B to SN-38-induced apoptosis. On the other hand, SN-38 phosphorylated Akt and pretreatment with PI3K inhibitors increased SN-38-induced apoptosis, indicating that resistance to SN-38 in Hep3B occurs partly through the PI3K/Akt not the NF-κB pathway. Blocking of PI3K/Akt may thus be helpful for overcoming chemo-resistance of HCC.

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May 2005
Volume 26 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Koizumi N, Hatano E, Nitta T, Tada M, Harada N, Taura K, Ikai I and Shimahara Y: Blocking of PI3K/Akt pathway enhances apoptosis induced by SN-38, an active form of CPT-11, in human hepatoma cells. Int J Oncol 26: 1301-1306, 2005
APA
Koizumi, N., Hatano, E., Nitta, T., Tada, M., Harada, N., Taura, K. ... Shimahara, Y. (2005). Blocking of PI3K/Akt pathway enhances apoptosis induced by SN-38, an active form of CPT-11, in human hepatoma cells. International Journal of Oncology, 26, 1301-1306. https://doi.org/10.3892/ijo.26.5.1301
MLA
Koizumi, N., Hatano, E., Nitta, T., Tada, M., Harada, N., Taura, K., Ikai, I., Shimahara, Y."Blocking of PI3K/Akt pathway enhances apoptosis induced by SN-38, an active form of CPT-11, in human hepatoma cells". International Journal of Oncology 26.5 (2005): 1301-1306.
Chicago
Koizumi, N., Hatano, E., Nitta, T., Tada, M., Harada, N., Taura, K., Ikai, I., Shimahara, Y."Blocking of PI3K/Akt pathway enhances apoptosis induced by SN-38, an active form of CPT-11, in human hepatoma cells". International Journal of Oncology 26, no. 5 (2005): 1301-1306. https://doi.org/10.3892/ijo.26.5.1301