多药耐药相关蛋白 2（MRP2）在食管鳞癌化疗耐药和临床结局中的作用。
Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma.
机构信息
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamada-oka, Suita, Osaka 565-0871, Japan.
出版信息
Br J Cancer. 2011 Feb 15;104(4):707-13. doi: 10.1038/sj.bjc.6606071. Epub 2011 Jan 4.
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.
背景
尽管多药耐药相关蛋白 2（MRP2）在某些癌症类型中赋予了化疗耐药性，但它在食管鳞状细胞癌（ESCC）中的意义尚不清楚。
方法
我们使用 81 例接受或未接受新辅助化疗（NACT）的 ESCC 患者的切除标本，通过免疫组织化学和 RT-PCR 评估了 MRP2 的表达，NACT 方案包括氟尿嘧啶、阿霉素和顺铂（CDDP）。还在 42 例治疗前活检样本和 8 个 ESCC 细胞系中研究了 MRP2 表达与化疗反应之间的相关性。
结果
接受 NACT 的 ESCC 中 MRP2 阳性免疫染色比未接受 NACT 的 ESCC 更为常见（27.3%比 5.4%）。MRP2 阳性患者的预后比 MRP2 阴性患者差（5 年生存率，25.6%比 55.7%）。一致地，接受 NACT 的 ESCC 中 MRP2 的 mRNA 表达比未接受 NACT 的 ESCC 高 2.1 倍（P=0.0350）。在接受 NACT 的患者的治疗前活检样本中，无反应者的 MRP2 mRNA 表达比有反应者高 2.9 倍（P=0.0035）。在 ESCC 细胞系中，TE14 表现出最高的 MRP2 mRNA 表达以及对 CDDP 的最强耐药性。通过小干扰 RNA 抑制 MRP2 表达降低了对 CDDP 的化疗耐药性。
结论
我们的数据表明，MRP2 是调节晚期 ESCC 患者对包括 CDDP 在内的化疗敏感性的分子之一。
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