Copper ions are novel therapeutic agents for uterine leiomyosarcoma
Copper ions are novel therapeutic agents for uterine leiomyosarcoma
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DOI：
10.1016/j.ajog.2019.07.030
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发表时间：
2020-01-01
影响因子：
9.8
通讯作者：
Kimura, Tadashi
中科院分区：
文献类型：
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作者：
Kakuda, Mamoru;Matsuzaki, Shinya;Kimura, Tadashi
背景：多药耐药是子宫平滑肌肉瘤治疗中的一个主要问题。开发有效的化疗药物和管理患者的耐药性是必要的。铜外排转运蛋白腺苷三磷酸酶铜转运β是P型腺苷三磷酸酶家族的成员，也被称为强铂外排转运蛋白。各种报道表明，腺苷三磷酸酶铜转运β和铂耐药之间的关联，然而，合适的抑制剂或抑制铂流出通过腺苷三磷酸酶铜转运beta.OBJECTIVE：我们的研究集中在子宫平滑肌肉瘤铂耐药。研究设计：采用Western印迹法检测腺苷三磷酸酶铜转运β在子宫平滑肌肉瘤对铂类药物耐药中的作用，并在体外和体内研究硫酸铜预处理和顺铂给药对腺苷三磷酸酶铜转运β表达细胞的作用。SK-LMS-1细胞（子宫平滑肌肉瘤细胞系）的蛋白质印迹分析揭示了强的腺苷三磷酸酶铜转运β表达。产生了永久性SK-LMS-ATP酶铜转运β抑制细胞系（SK-LMS-7 B细胞），顺铂在SK-LMS-7 B细胞中表现出显著的抗肿瘤作用，在体外（SK-LMS-1细胞，半最大抑制浓度，17.2 mM; SK-LMS-7 B细胞，半最大抑制浓度，4.2 mM，P
BACKGROUND: Multidrug resistance is a major concern in uterine leiomyosarcoma treatment. Development of effective chemotherapies and management of drug resistance in patients is necessary. The copper efflux transporter adenosine triphosphatase copper transporting beta is a member of the P-type adenosine triphosphatase family and is also known as a strong platinum efflux transporter. Various reports have shown the association between adenosine triphosphatase copper transporting beta and platinum resistance; however, suitable inhibitors or methods for inhibiting platinum efflux via adenosine triphosphatase copper transporting beta are not developed.OBJECTIVE: Our study focused on platinum resistance in uterine leiomyosarcoma. The role of adenosine triphosphatase copper transporting beta in uterine leiomyosarcoma resistance to platinum drugs was investigated both in vitro and in vivo.STUDY DESIGN: Adenosine triphosphatase copper transporting beta expression was investigated by Western blotting and the efficacy of copper sulfate pretreatment and cisplatin administration in adenosine triphosphatase copper transporting betaeexpressing cells was investigated both in vitro and in vivo.RESULTS: Western blot analysis of SK-LMS-1 cells (uterine leiomyosarcoma cell line) revealed strong adenosine triphosphatase copper transporting beta expression. A permanent SK-LMS-ATPase copper transporting betaesuppressed cell line (SK-LMS-7B cells) was generated, and cisplatin exhibited a significant antitumor effect in SK-LMS-7B cells, both in vitro (SK-LMS-1 cells, half-maximal inhibitory concentration, 17.2 mM; SK-LMS-7B cells, half-maximal inhibitory concentration, 4.2 mM, P