Beneficial effect of cepharanthine on overcoming drug-resistance of hepatocellular carcinoma

  • Authors:
    • Akio Nakajima
    • Yuzo Yamamoto
    • Kojiro Taura
    • Koichiro Hata
    • Manabu Fukumoto
    • Hiroshi Uchinami
    • Kei Yonezawa
    • Yoshio Yamaoka
  • View Affiliations

  • Published online on: March 1, 2004     https://doi.org/10.3892/ijo.24.3.635
  • Pages: 635-645
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Abstract

Despite improvement in liver surgery, patient prognoses after surgical resection for hepatocellular carcinoma (HCC) remain unsatisfactory. One of the obstacles in managing post-operative recurrence is resistance to chemotherapy. We examined the effect of Cepharanthin™ (CEP), a natural alkaloid extracted from Stephania cepharantha Hayata, in overcoming P-glycoprotein (P-gp)-associated doxorubicine (DOX) resistance, using 2 DOX-resistant HCC cell lines, and their DOX-sensitive parental cell lines. P-gp expression in surgically removed HCC tumours was also examined. In the in vitro study, overexpression of P-gp in the resistant cells was confirmed by immunoblotting and RT-PCR. Drug sensitivity testing with MTT assay showed that co-administration of CEP significantly enhanced cytotoxicity of DOX, but only in resistant cells. Flow cytometric analysis revealed that CEP significantly increased intracellular DOX concentration by inhibiting DOX efflux. P-gp expression in 107 patients with HCC was examined retrospectively by immunohistochemistry. P-gp was overexpressed in the tumours of 36% of these patients, especially in well-differentiated tumours that are often insensitive to chemotherapy, supporting the use of P-gp modulation as a new chemotherapeutic approach. Multivariate logistic regression analysis revealed that serum α-fetoprotein level was inversely related to P-gp expression. Our data suggest that co-administration of CEP with DOX may potentiate the effect of chemotherapy on drug-resistant HCC.

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March 2004
Volume 24 Issue 3

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

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APA
Nakajima, A., Yamamoto, Y., Taura, K., Hata, K., Fukumoto, M., Uchinami, H. ... Yamaoka, Y. (2004). Beneficial effect of cepharanthine on overcoming drug-resistance of hepatocellular carcinoma. International Journal of Oncology, 24, 635-645. https://doi.org/10.3892/ijo.24.3.635
MLA
Nakajima, A., Yamamoto, Y., Taura, K., Hata, K., Fukumoto, M., Uchinami, H., Yonezawa, K., Yamaoka, Y."Beneficial effect of cepharanthine on overcoming drug-resistance of hepatocellular carcinoma". International Journal of Oncology 24.3 (2004): 635-645.
Chicago
Nakajima, A., Yamamoto, Y., Taura, K., Hata, K., Fukumoto, M., Uchinami, H., Yonezawa, K., Yamaoka, Y."Beneficial effect of cepharanthine on overcoming drug-resistance of hepatocellular carcinoma". International Journal of Oncology 24, no. 3 (2004): 635-645. https://doi.org/10.3892/ijo.24.3.635