Chappell William H, Abrams Stephen L, Montalto Giuseppe, Cervello Melchiorre, Martelli Alberto M, Candido Saverio, Libra Massimo, Polesel Jerry, Talamini Renato, Arlinghaus Ralph, Steelman Linda S, McCubrey James A
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Oncotarget. 2012 Oct;3(10):1236-45. doi: 10.18632/oncotarget.691.
Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the lipocalin family which has diverse roles including stabilizing matrix metalloproteinase-9 from auto-degradation and as siderocalins which are important in the transport of iron. NGAL also has important biological functions involved in immunity and inflammation as well as responses to kidney damage. NGAL expression has also been associated with certain neoplasia and is important in the metastasis of breast cancer. Many advanced cancer patients have elevated levels of NGAL in their urine and it has been proposed that NGAL may be a prognostic indicator for certain cancers (e.g. breast, brain, and others). NGAL expression is detected in response to various chemotherapeutic drugs including doxorubicin and docetaxel. We were interested in the roles of NGAL expression in cancer and whether it is associated with chemotherapeutic drug resistance. In the present study, we investigated whether increased NGAL expression led to resistance to the chemotherapeutic drug doxorubicin in normal breast epithelial cells (MCF-10A), breast cancer cells (MCF-7), and colorectal cancer cells (HT-29). We infected the various cell lines with a retrovirus encoding NGAL which we constructed. Increased NGAL expression was readily detected in the NGAL-infected cells but not the empty vector-infected cells. However, increased NGAL expression did not alter the sensitivity of the cells to the chemotherapeutic drug doxorubicin. Thus, although NGAL expression is often detected after chemotherapeutic drug treatment, it by itself, does not lead to doxorubicin resistance.
中性粒细胞明胶酶相关脂质运载蛋白（NGAL，又名Lnc2）是脂质运载蛋白家族的成员，具有多种作用，包括稳定基质金属蛋白酶-9使其免于自降解，以及作为在铁运输中起重要作用的铁转运蛋白。NGAL还具有参与免疫和炎症以及对肾损伤反应的重要生物学功能。NGAL的表达也与某些肿瘤形成有关，并且在乳腺癌转移中起重要作用。许多晚期癌症患者尿液中NGAL水平升高，有人提出NGAL可能是某些癌症（如乳腺癌、脑癌等）的预后指标。在对包括阿霉素和多西他赛在内的各种化疗药物的反应中可检测到NGAL表达。我们对NGAL表达在癌症中的作用以及它是否与化疗耐药性相关感兴趣。在本研究中，我们调查了NGAL表达增加是否会导致正常乳腺上皮细胞（MCF-10A）、乳腺癌细胞（MCF-7）和结肠癌细胞（HT-29）对化疗药物阿霉素产生耐药性。我们用我们构建的编码NGAL的逆转录病毒感染了各种细胞系。在感染NGAL的细胞中很容易检测到NGAL表达增加，而在感染空载体的细胞中则未检测到。然而，NGAL表达增加并未改变细胞对化疗药物阿霉素的敏感性。因此，尽管在化疗药物治疗后经常检测到NGAL表达，但它本身并不会导致对阿霉素的耐药性。
