Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as gefitinib are standard treatment of non-small cell lung cancer (NSCLC), but resistance often occurs. This study demonstrates that NSCLC cells resistant to gefitinib (GR cells) displayed a significantly higher microsomal prostaglandin E synthase-1 (mPGES-1) expression and activity than parental cells. Overexpression of mPGES-1/prostaglandin E-2 (PGE-2) signaling in GR cells was associated with acquisition of mesenchymal and stem-like cell properties, nuclear EGFR translocation and tolerance to cisplatin. mPGES-1 inhibition reduced mesenchymal and stem-like properties, and nuclear EGFR translocation in GR cells. Consistently, inhibition of mPGES-1 activity enhanced sensitivity to cisplatin and responsiveness to gefitinib in GR cells. We propose the mPGES-1/PGE-2 signaling as a potential target for treating aggressive and resistant lung cancers.

中文翻译：

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mPGES-1作为克服非小细胞肺癌细胞系对吉非替尼的获得性耐药性的新靶标。

作为吉非替尼的表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）是非小细胞肺癌（NSCLC）的标准治疗方法，但经常会产生耐药性。这项研究表明，对吉非替尼具有抗药性的NSCLC细胞（GR细胞）显示出比亲代细胞明显更高的微粒体前列腺素E合酶1（mPGES-1）表达和活性。GR细胞中mPGES-1 /前列腺素E-2（PGE-2）信号的过度表达与间充质和干样细胞特性的获得，核EGFR易位以及对顺铂的耐受性有关。mPGES-1抑制降低了GR细胞中的间充质和茎样特性以及核EGFR易位。一致地，在GR细胞中，抑制mPGES-1活性可增强对顺铂的敏感性和对吉非替尼的反应性。