Image-based chemical screening identifies drug efflux inhibitors in lung cancer cells.
Image-based chemical screening identifies drug efflux inhibitors in lung cancer cells.
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DOI：
10.1158/0008-5472.can-09-4360
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发表时间：
2010-10-01
期刊：
影响因子：
11.2
通讯作者：
Wong ST
中科院分区：
文献类型：
--
作者：
Xia X;Yang J;Li F;Li Y;Zhou X;Dai Y;Wong ST
具有主动药物流出能力的癌细胞具有多重耐药性，对化疗的疗效构成重大障碍。此外，最近的证据表明，高药物流出癌细胞（HDECC）可能选择性地富含干细胞样癌细胞，这被认为是肿瘤发生和复发的原因。非常需要能够消除 HDECC 的治疗试剂。我们开发了一种基于图像的高内涵筛选 (HCS) 系统，用于专门识别和分析肺癌细胞中的 HDECC 群体。使用该系统，我们筛选了 1,280 种具有药理活性的化合物，其中鉴定出 12 种有效的 HDECC 抑制剂。结果表明，这些抑制剂能够克服MDR并使HDECC对化疗药物敏感，或者可能通过影响干细胞样癌细胞来直接降低肺癌细胞的致瘤性。我们建立的HCS系统为识别克服MDR的治疗试剂提供了一种新方法。通过筛选鉴定的化合物有可能用作潜在的佐剂，以提高化疗药物的疗效。
Cancer cells with active drug-efflux capability are multidrug resistant and pose a significant obstacle for the efficacy of chemotherapy. Moreover, recent evidence suggests that high drug-efflux cancer cells (HDECCs) may be selectively enriched with stem-like cancer cells, which are believed to be the cause for tumor initiation and recurrence. There is a great need for therapeutic reagents that are capable of eliminating HDECCs. We developed an image-based high-content screening (HCS) system to specifically identify and analyze the HDECC population in lung cancer cells. Using the system, we screened 1,280 pharmacologically active compounds which identified twelve potent HDECC inhibitors. It is shown that these inhibitors are able to overcome MDR and sensitize HDECCs to chemotherapeutic drugs, or directly reduce the tumorigenicity of lung cancer cells possibly by affecting stem-like cancer cells. The HCS system we established provides a new approach for identifying therapeutic reagents overcoming MDR. The compounds identified by the screening may potentially be used as potential adjuvant to improve the efficacy of chemotherapeutic drugs.