論文

査読有り 国際誌
2004年

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

International journal of oncology
  • Nakajima, A.
  • ,
  • Yamamoto, Y.
  • ,
  • Taura, K.
  • ,
  • Hata, K.
  • ,
  • Fukumoto, M.
  • ,
  • Uchinami, H.
  • ,
  • Yonezawa, K.
  • ,
  • Yamaoka, Y.

24
3
開始ページ
635
終了ページ
45
記述言語
英語
掲載種別
研究論文(学術雑誌)
出版者・発行元
PROFESSOR D A SPANDIDOS

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 alpha-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.

リンク情報
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/14767548
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000188956800019&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-6044228068&partnerID=MN8TOARS
ID情報
  • ISSN : 1019-6439
  • ORCIDのPut Code : 74839368
  • PubMed ID : 14767548
  • SCOPUS ID : 6044228068
  • Web of Science ID : WOS:000188956800019

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