2004年
Beneficial effect of cepharanthine on overcoming drug-resistance of hepatocellular carcinoma.
International journal of oncology
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- 巻
- 24
- 号
- 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
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- 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
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- ISSN : 1019-6439
- ORCIDのPut Code : 74839368
- PubMed ID : 14767548
- SCOPUS ID : 6044228068
- Web of Science ID : WOS:000188956800019