Nishi Koji, Kato Megumi, Sakurai Saki, Matsumoto Ayako, Iwase Yumiko, Yumita Nagahiko
Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Kanagawa, Japan
Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Kanagawa, Japan.
Anticancer Res. 2017 Nov;37(11):6211-6214. doi: 10.21873/anticanres.12071.
Pancreatic cancer is one of the deadliest human cancers. In the current study, we investigated the possibility of a new treatment strategy using a combination of the new fluoroquinolone, enoxacin, and mild ultraviolet A (UVA) irradiation. Enoxacin with UVA irradiation increased the number of annexin V-positive (apoptotic) pancreatic cancer cells in time- and concentration-dependent manners, whereas alone neither had these effects. In addition, enoxacin with UVA irradiation induced cleavage of poly (ADP-ribose) polymerase in AsPC1 human pancreatic cancer cells. Moreover, the singlet oxygen scavengers, histidine and sodium azide, and the hydroxyl radical scavenger, mannitol, significantly suppressed apoptosis induced by enoxacin and UVA irradiation, respectively. These results suggest that UVA irradiation activates enoxacin, after which activated enoxacin induces apoptosis of AsPC1 cells through generation of reactive oxygen species. Therefore, the combination of enoxacin with mild UVA irradiation may be a useful method for treating pancreatic cancer.
胰腺癌是人类最致命的癌症之一。在当前的研究中，我们研究了一种新的治疗策略的可能性，该策略使用新型氟喹诺酮类药物依诺沙星和温和的紫外线A（UVA）照射相结合。依诺沙星与UVA照射以时间和浓度依赖性方式增加了膜联蛋白V阳性（凋亡）胰腺癌细胞的数量，而单独使用两者均无这些作用。此外，依诺沙星与UVA照射诱导了AsPC1人胰腺癌细胞中聚（ADP-核糖）聚合酶的裂解。此外，单线态氧清除剂组氨酸和叠氮化钠以及羟基自由基清除剂甘露醇分别显著抑制了依诺沙星和UVA照射诱导的细胞凋亡。这些结果表明，UVA照射激活了依诺沙星，之后激活的依诺沙星通过产生活性氧诱导AsPC1细胞凋亡。因此，依诺沙星与温和的UVA照射相结合可能是治疗胰腺癌的一种有用方法。
