論文 - 詳細
| RRC ID | 55977 |
|---|---|
| 著者 | Wada F, Koga H, Akiba J, Niizeki T, Iwamoto H, Ikezono Y, Nakamura T, Abe M, Masuda A, Sakaue T, Tanaka T, Kakuma T, Yano H, Torimura T. |
| タイトル | High expression of CD44v9 and xCT in chemoresistant hepatocellular carcinoma: Potential targets by sulfasalazine. |
| ジャーナル | Cancer Sci |
| Abstract |
CD44v9 is expressed in cancer stem cells (CSC) and stabilizes the glutamate-cystine transporter xCT on the cytoplasmic membrane, thereby decreasing intracellular levels of reactive oxygen species (ROS). This mechanism confers ROS resistance to CSC and CD44v9-expressing cancer cells. The aims of the present study were to assess: (i) expression status of CD44v9 and xCT in hepatocellular carcinoma (HCC) tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization (HAIC) therapy with cisplatin (CDDP); and (ii) whether combination of CDDP with sulfasalazine (SASP), an inhibitor of xCT, was more effective on tumor cells than CDDP alone by inducing ROS-mediated apoptosis. Twenty non-pretreated HCC tissues and 7 HCC tissues administered HAIC therapy with CDDP before surgical resection were subjected to immunohistochemistry analysis of CD44v9 and xCT expression. Human HCC cell lines HAK-1A and HAK-1B were used in this study; the latter was also used for xenograft experiments in nude mice to assess in vivo efficacy of combination treatment. CD44v9 positivity was significantly higher in HAIC-treated tissues (5/7) than in non-pretreated tissues (2/30), suggesting the involvement of CD44v9 in the resistance to HAIC. xCT was significantly expressed in poorly differentiated HCC tissues. Combination treatment effectively killed the CD44v9-harboring HAK-1B cells through ROS-mediated apoptosis and significantly decreased xenografted tumor growth. In conclusion, the xCT inhibitor SASP augmented ROS-mediated apoptosis in CDDP-treated HCC cells, in which the CD44v9-xCT system functioned. As CD44v9 is typically expressed in HAIC-resistant HCC cells, combination treatment with SASP with CDDP may overcome such drug resistance. |
| 巻・号 | 109(9) |
| ページ | 2801-2810 |
| 公開日 | 2018-9-1 |
| DOI | 10.1111/cas.13728 |
| PMID | 29981246 |
| PMC | PMC6125439 |
| MeSH | Aged Aged, 80 and over Amino Acid Transport System y+ / analysis Amino Acid Transport System y+ / physiology* Animals Apoptosis / drug effects Carcinoma, Hepatocellular / chemistry Carcinoma, Hepatocellular / drug therapy* Cisplatin / pharmacology Drug Resistance, Neoplasm Female Hep G2 Cells Humans Hyaluronan Receptors / analysis Hyaluronan Receptors / physiology* Liver Neoplasms / chemistry Liver Neoplasms / drug therapy* Male Mice Mice, Inbred BALB C Middle Aged Reactive Oxygen Species / metabolism Sulfasalazine / pharmacology* |
| IF | 4.751 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HCT116(RCB2979) |