Establishment and molecular profiling of a novel human pancreatic cancer panel for 5-FU
Establishment and molecular profiling of a novel human pancreatic cancer panel for 5-FU
复制标题
DOI：
10.1111/j.1349-7006.2008.00896.x
复制
发表时间：
2008-09-01
期刊：
影响因子：
5.7
通讯作者：
Nishio, Kazuto
中科院分区：
文献类型：
--
作者：
Yanagihara, Kazuyoshi;Takigahira, Misato;Nishio, Kazuto
从可移植的胰腺癌细胞系建立了10个新的人胰腺癌细胞系（Sui 65至Sui 74）。所有细胞系在形态学和生物学特征上均与原始临床癌相似，存在基因改变，如K-ras和p53点突变，SMAD 4和p16减弱或缺失以及其他相关细胞特征。利用该面板，我们评估了5-FU在抑制胰腺癌细胞增殖中的作用。在体外测试时，尽管Sui 72对5-FU高度敏感，但发现其他细胞系对该药物具有耐药性。当将Sui 72和Sui 70皮下植入SCID小鼠，然后用5-FU治疗时，发现药物对Sui 72有效，但对Sui 70无效，与体外结果一致。为了确定Sui 72对5-FU高敏感性的分子决定因素，我们检测了5-FU代谢酶的mRNA表达水平。与其他细胞系相比，在Sui 72中观察到DPYD表达降低（0.1对0.6 +/-0.5，0.1倍）。
Ten novel human pancreatic carcinoma cell lines (Sui65 through Sui74) were established from a transplantable pancreatic carcinoma cell line. All the cell lines resembled the original clinical carcinoma in terms of the morphological and biological features, presenting with genetic alterations such as point mutations of K-ras and p53, attenuation or lack of SMAD4 and p16 and other relevant cellular characteristics. Using this panel, we evaluated the effects of 5-FU in suppressing the proliferation of pancreatic carcinoma cells. When tested in vitro, although Sui72 was highly susceptible to 5-FU, the other cell lines were found to be resistant to the drug. When Sui72 and Sui70 were implanted subcutaneously in SCID mice followed by treatment with 5-FU, the drug was found to be effective against Sui72 but not Sui70, consistent with the results in vitro. In order to identify the molecular determinant for high sensitivity of Sui72 to 5-FU, we examined the mRNA expression levels of the metabolic enzymes of 5-FU. Decreased expression of DPYD was observed in Sui72 as compared with other cell lines (0.1 versus 0.6 +/- 0.5, 0.1-fold).It is believed that the novel cell lines established in the present study will be useful for analyzing the pattern of progression of pancreatic cancer and for evaluating the efficacy of anticancer agents.