論文 - 詳細
| RRC ID | 38451 |
|---|---|
| 著者 | Yamasaki M, Makino T, Masuzawa T, Kurokawa Y, Miyata H, Takiguchi S, Nakajima K, Fujiwara Y, Matsuura N, Mori M, Doki Y. |
| タイトル | Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS:We evaluated MRP2 expression by immunohistochemistry and RT-PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was also examined in 42 pre-therapeutic biopsy samples and eight ESCC cell lines. RESULTS:MRP2-positive immunostaining was more frequently observed in ESCCs with NACT than in those without NACT (27.3 vs 5.4%). The MRP2-positive patients showed poorer prognosis than MRP2-negative patients (5-year survival rate, 25.6 vs 55.7%). Concordantly, ESCC with NACT showed 2.1-fold higher mRNA expression of MRP2 than those without NACT (P=0.0350). In pre-therapeutic biopsy samples of patients with NACT, non-responders showed 2.9-fold higher mRNA expression of MRP2 than responders (P=0.0035). Among the panel of ESCC cell lines, TE14 showed the highest MRP2 mRNA expression along with the strongest resistance to CDDP. Inhibition of MRP2 expression by small-interfering RNA reduced chemoresistance to CDDP. CONCLUSION:Our data suggested that MRP2 is one of molecules, which regulate the sensitivity to chemotherapy including CDDP in advanced ESCC patients. |
| 巻・号 | 104(4) |
| ページ | 707-13 |
| 公開日 | 2011-2-15 |
| DOI | 10.1038/sj.bjc.6606071 |
| PII | 6606071 |
| PMID | 21206495 |
| PMC | PMC3049584 |
| MeSH | Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols / therapeutic use Biomarkers, Pharmacological / analysis Biomarkers, Pharmacological / metabolism Biomarkers, Tumor / analysis Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / mortality Cell Line, Tumor Cisplatin / administration & dosage Doxorubicin / administration & dosage Drug Resistance, Multiple / drug effects Drug Resistance, Multiple / genetics Drug Resistance, Neoplasm / drug effects Drug Resistance, Neoplasm / genetics* Esophageal Neoplasms / drug therapy Esophageal Neoplasms / genetics* Esophageal Neoplasms / metabolism Esophageal Neoplasms / mortality Female Fluorouracil / administration & dosage Gene Expression Regulation, Neoplastic / drug effects Humans Immunohistochemistry Male Middle Aged Multidrug Resistance-Associated Protein 2 Multidrug Resistance-Associated Proteins / genetics Multidrug Resistance-Associated Proteins / metabolism Multidrug Resistance-Associated Proteins / physiology* Neoadjuvant Therapy RNA, Small Interfering / pharmacology Survival Analysis |
| IF | 5.791 |
| 引用数 | 73 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | TE-1(RCB1894) TE-5(RCB1949) TE-6(RCB1950) TE-9(RCB1988) TE-10(RCB2099) TE-11(RCB2100) TE-14(RCB2101) TE-15(RCB1951) |