Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma
Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma
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DOI：
10.1016/j.bbrc.2015.01.035
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发表时间：
2015-02-20
影响因子：
3.1
通讯作者：
Wang, Qiming
中科院分区：
文献类型：
--
作者：
Wu, Yufeng;Si, Ruirui;Wang, Qiming
不能手术的肺腺癌目前采用含铂化疗。然而，这些化疗药物的有效性对所有患者并不相同。患者表现出快速耐药（QCR）或延迟耐药（DCR），分别定义为初始铂类药物治疗后的87天和242天无进展生存期（IFS）。我们发现，QCR患者显示血清胆固醇水平升高，他们的肿瘤显示ABCG 2表达上调。我们认为化疗耐药性可能是由于胆固醇诱导的ABCG2表达，并假设阻断ABCG2可能会增加铂类化疗药物的疗效。使用MTT细胞活力测定，我们观察到ABCG 2黑剂尼卡地平和铂类药物顺铂、奥沙利铂或卡铂的共处理显著降低肿瘤细胞的细胞活力。重要的是，我们的研究结果还表明，在化疗治疗或共治疗之前，将细胞与胆固醇一起孵育，相对于对照组，增加了肿瘤细胞的细胞活力。(C)2015 Elsevier Inc. All rights reserved.
Inoperable lung adenocarcinoma is currently treated with platinum-based chemotherapy. However, the effectiveness of these chemotherapeutic agents is not the same for all patients. Patients either show quick chemoresistance (QCR) or delayed chemoresistance (DCR), which are defined by 87 and 242 days of progression-free survival (IFS) after initial platinum-based treatment, respectively. We found that QCR patients displayed an elevated level of serum cholesterol and that their tumors showed upregulated ABCG2 expression. We propose that chemoresistance may be attributed to cholesterol-induced ABCG2 expression and hypothesize that blocking ABCG2 may increase the efficacy of platinum-based chemotherapeutic agents. Using the MTT cell viability assay, we observed that cotreatment with ABCG2 blacker Nicardipine and platinum-based drugs Cisplatin, Oxaliplatin or Carboplatin significantly decreased cell viability of tumor cells. Importantly, our results also showed that incubating cells with cholesterol prior to chemotherapy treatment or cotreatment increased cell viability of tumor cells relative to the controls. (C) 2015 Elsevier Inc. All rights reserved.