In vitro and in vivo evidence that a combination of lapatinib plus S-1 is a promising treatment for pancreatic cancer
In vitro and in vivo evidence that a combination of lapatinib plus S-1 is a promising treatment for pancreatic cancer
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DOI：
10.1111/j.1349-7006.2009.01405.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.7
通讯作者：
Hirakawa, Kosei
中科院分区：
文献类型：
--
作者：
Komoto, Masahiro;Nakata, Bunzo;Hirakawa, Kosei
拉帕替尼是HER 2和表皮生长因子受体（EGFR）的小分子抑制剂。我们研究了拉帕替尼单独或与氟嘧啶衍生物S-1联合治疗胰腺癌的效果。通过流式细胞术测量四种胰腺癌细胞系MiaPaca-2、PANC-1、Capan-1和Capan-2中的每一种中的HER 2/EGFR表达。使用这四种细胞系生成的雌性BALB/c裸鼠异种移植物评价拉帕替尼（30 mg/kg）和/或S-1（10 mg/kg）的抗肿瘤作用。通过体外中位效应分析检查拉帕替尼与S-1之间的协同作用。用抗人HER 2和EGFR抗体对来自137名患者的切除的胰腺癌组织进行免疫化学染色。拉帕替尼作为单一药物给药基本上抑制了所有检查的胰腺癌细胞系的体内肿瘤生长。在HER 2表达和拉帕替尼的体内抗肿瘤作用之间观察到强相关性。拉帕替尼与S-1协同抑制MiaPaca-2和PANC-1异种移植物的肿瘤生长。当在体外作为单一药物使用时，拉帕替尼几乎不抑制任何细胞系的细胞生长。然而，拉帕替尼与S-1组分5-氟尿嘧啶和5-氯-2，4-二氢酶对所有细胞系的抗肿瘤活性具有协同作用。免疫组化染色显示70%的胰腺癌过表达HER 2和/或EGFR。拉帕替尼单药治疗和与S-1联合治疗可能是胰腺癌患者有希望的治疗方法;大多数这些癌症表达拉帕替尼靶分子。（Cancer Sci 2010; 101：468-473）
Lapatinib is a small molecule inhibitor of both HER2 and the epidermal growth factor receptor ( EGFR). We investigated the effect of treatment with lapatinib alone or in combination with a fluoropyrimidine derivative S-1 against pancreatic cancer. The HER2/EGFR expression in each of the four pancreatic cancer cell lines MiaPaca-2, PANC-1, Capan-1 and Capan-2 was measured by flow cytometry. The anti-tumor effects of lapatinib (30 mg/kg) and/or S-1 (10 mg/kg) were evaluated using female BALB/c nude mice xenografts generated using these four cell lines. Synergy between lapatinib and S-1 was examined by median effect analysis in vitro. Resected pancreatic cancer tissues from 137 patients were immunohistochemically stained with anti-human HER2 and EGFR antibodies. The administration of lapatinib as a single agent substantially suppressed tumor growth in vivo of all pancreatic cancer cell lines examined. A strong correlation was observed between HER2 expression and the anti-tumor effect of lapatinib in vivo. Lapatinib synergized with S-1 to inhibit the tumor growth of MiaPaca-2 and PANC-1 xenografts. When used as a single agent in vitro, lapatinib barely inhibit the cell growth of any cell line. However, lapatinib synergized with the anti-tumor activity of the S-1 components 5-fluorouracil and 5-chloro-2,4-dihydrogenase against all cell lines. Immunohistochemical staining demonstrated that 70% of the pancreatic cancers overexpressed HER2 and/or EGFR. Both lapatinib monotherapy and combined treatment with S-1 may be promising treatments for patients with pancreatic cancers; the majority these cancers express lapatinib target molecules. (Cancer Sci 2010; 101: 468-473)