Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine.
Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine.
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DOI：
10.3892/ijo.31.6.1345
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发表时间：
2007-12
影响因子：
5.2
通讯作者：
Sayaka Mori-Iwamoto;Y. Kuramitsu;S. Ryozawa;Kuniko Mikuria;M. Fujimoto;S. Maehara;Y. Maehara;K. Oki
中科院分区：
文献类型：
--
作者：
Sayaka Mori-Iwamoto;Y. Kuramitsu;S. Ryozawa;Kuniko Mikuria;M. Fujimoto;S. Maehara;Y. Maehara;K. Oki
胰腺癌仍然是一种毁灭性的疾病，>96% 的胰腺癌患者存活时间不能超过 5 年。吉西他滨（2'-脱氧-2'-二氟-脱氧胞苷：Gemzar）似乎是临床上唯一有效治疗胰腺癌的药物，但对预后影响不大。对吉西他滨敏感细胞 (KLM1) 和耐药胰腺细胞 (KLM1-R) 进行蛋白质组学分析，以鉴定吉西他滨的靶蛋白。我们发现了 7 种蛋白质：HSP27、过氧化还原蛋白 2、内质网蛋白 ERp29 前体、6-磷酸葡萄糖酸内酯酶、三磷酸异构酶、α 烯醇酶和核磷胺，它们可能在确定胰腺癌对吉西他滨的敏感性中发挥作用。我们敲低了 KLM1-R 中的 HSP27，恢复了对吉西他滨的敏感性。此外，肿瘤标本中HSP27表达增加与胰腺癌患者对吉西他滨较高的耐药性有关。 HSP27可能在对吉西他滨的耐药性中发挥重要作用，并且它也可能成为预测胰腺癌患者对吉西他滨治疗反应的可能生物标志物。
Pancreatic cancer remains a devastating disease and >96% of patients with pancreatic cancer do not survive for more than 5 years. Gemcitabine (2'-deoxy-2'-difluoro-deoxycytidine: Gemzar) appears to be the only clinically effective drug for pancreatic cancer, but it has little impact on outcome. Proteomic analysis of gemcitabine-sensitive cells (KLM1) and resistant pancreatic cells (KLM1-R) was performed to identify target proteins of the gemcitabine. We found seven proteins, HSP27, peroxiredoxin 2, endoplasmic reticulum protein ERp29 precursor, 6-phosphogluconolactonase, triosphospate isomerase, alpha enolase, and nucleophosmine that could play a role in determining the sensitivity of pancreatic cancer to gemcitabine. We knocked down HSP27 in KLM1-R and the sensitivity to gemcitabine was restored. In addition, increased HSP27 expression in tumor specimens was related to higher resistibility to gemcitabine in patients of pancreatic cancer. HSP27 may play an important role in the resistibility to gemcitabine, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with gemcitabine.