Anticancer effects of non-steroidal anti-inflammatory drugs against cancer cells and cancer stem cells
Anticancer effects of non-steroidal anti-inflammatory drugs against cancer cells and cancer stem cells
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DOI：
10.1016/j.tiv.2021.105155
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发表时间：
2021-04-02
影响因子：
3.2
通讯作者：
Kobayashi, Masaki
中科院分区：
文献类型：
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作者：
Okamoto, Keisuke;Saito, Yoshitaka;Kobayashi, Masaki
已知某些非甾体抗炎药（NSAID）具有抗癌作用。然而，目前还不清楚是否所有的NSAID都有抗癌作用，到目前为止，很少有研究比较多种NSAID之间的抗肿瘤作用。因此，我们的目的是确定非甾体抗炎药，提高顺铂（CDDP）的抗癌作用，17非甾体抗炎药在肺癌细胞及其球体作为癌症干细胞（CSC）的影响进行了评价。部分NSAID对A549和SBC-3细胞及其耐顺铂细胞系（分别为A549/DDP和SBC-3/DDP细胞）显示出细胞毒作用。此外，CDDP和塞来昔布的共同添加，表现出细胞毒性作用，通过增加A549/DDP和SBC-3/DDP细胞中的SLC 7A 11（这是CDDP耐药机制之一）来增加对CDDP的耐药性。另一方面，塞来昔布对A549/DDP和SBC-3/DDP细胞的球状体也显示出抗肿瘤作用，并增强CDDP的抗肿瘤作用，同时增加SLC 7A 11的mRNA水平。此外，双氯芬酸也具有细胞毒性，可增强CDDP对癌细胞和CSC的细胞毒性作用。结论：塞来昔布和双氯芬酸等非甾体抗炎药可增强顺铂的疗效。
Certain non-steroidal anti-inflammatory drugs (NSAIDs) are known to have anticancer effects. However, it is unclear whether all NSAIDs have anticancer effects, and thus far, very few studies have compared the antitumor effects among multiple NSAIDs. Therefore, we aimed to identify NSAIDs that enhance the anticancer effect of cisplatin (CDDP); the effects of 17 NSAIDs in lung cancer cells and their spheroids as cancer stem cells (CSCs) were evaluated. Some of the NSAIDs showed cytotoxic effects against A549 and SBC-3 cells and their CDDPresistant cell lines (A549/DDP and SBC-3/DDP cells, respectively). In addition, co-addition of CDDP and celecoxib, which showed cytotoxic effects, increased the resistance to CDDP by increasing SLC7A11, which is one of the CDDP resistance mechanisms, in A549/DDP and SBC-3/DDP cells. On the other hand, celecoxib also showed antitumor effects on the spheroids of A549/DDP and SBC-3/DDP cells, and enhanced the antitumor effect of CDDP while increasing the mRNA levels of SLC7A11. Moreover, diclofenac was also cytotoxic and enhanced the cytotoxic effect of CDDP in cancer cells and CSCs. In conclusion, some NSAIDs including celecoxib and diclofenac may enhance the therapeutic efficacy of CDDP.