天然产物西红花苷靶向TMEM16A离子通道治疗肺腺癌机制研究  

Mechanism of natural product crocin in the treatment of lung adenocarcinoma targeting TMEM16A ion channel

作　　者：白雪 穆淑梅[1] 张伟伟[1] 张晗[1] 郭帅 BAI Xue;MU ShuMei;ZHANG WeiWei;ZHANG Han;GUO Shuai(School of Life Sciences,Hebei University,Baoding 071002,China)

机构地区：[1]河北大学生命科学学院,保定071002

出　　处：《中国科学：生命科学》2021年第9期1299-1307,共9页Scientia Sinica(Vitae)

基　　金：河北省自然科学基金(批准号:C2021201025);河北大学高层次人才科研启动项目(批准号:521000981428)资助。

摘　　要：TMEM16A离子通道在人体各种生理活动中起着至关重要的作用,并且是多种疾病的潜在药物靶点.最近,多项研究表明,TMEM16A在肺癌中内源性高表达与肺癌细胞增殖、迁移密切相关.本研究发现,西红花苷是一种新的TMEM16A天然产物抑制剂,它可以通过抑制TMEM16A从而抑制肺癌细胞增殖和迁移.本团队的研究数据表明,西红花苷浓度依赖性抑制TMEM16A全细胞电流,其IC50值约为(38.32±2.31)μmol/L.CCK8和划痕愈伤实验表明,西红花苷浓度依赖性抑制肺癌细胞LA795和NCI-H1299的增殖和迁移,但是对肺胚二倍体细胞2BS的增殖和迁移几乎没有抑制作用.利用shRNA敲除内源性TMEM16A可以消除西红花苷对LA795细胞增殖和迁移的抑制效果.总之,本研究提示TMEM16A是西红花苷抑制肺癌增殖和迁移的潜在作用靶点,西红花苷可以作为肺癌治疗药物的先导化合物进行研究.TMEM16A plays a vital role in various physiological activities in the human body,and it is a potential drug target for many diseases.Recently,several studies have shown that the high expression of TMEM16A in lung cancer is closely related to the proliferation and migration of lung cancer cells.This work demonstrates that crocin is a new natural-product inhibitor of TMEM16A and it can inhibit the proliferation and migration of lung cancer cells through TMEM16A.Our results showed that crocin inhibits TMEM16A wholecell currents in a concentration-dependent manner with an IC50 value of(38.32±2.31)μmol/L.CCK8 and wound healing studies showed that crocin inhibits the proliferation and migration of lung cancer cells LA795 and NCI-H1299 in a concentration-dependent manner;however,it does not affect the proliferation and migration of 2 BS cells.In addition,the inhibitory effect of crocin on the proliferation and migration of LA795 cells can be overcome by knockdown of TMEM16A using sh RNA.In conclusion,this work suggests that TMEM16A is a potential drug target of crocin as it can inhibit the proliferation and migration of lung cancer.Crocin can be further evaluated as an intriguing lead for lung cancer treatment.

关 键 词：西红花苷 肺癌 TMEM16A 药物靶点 抑制剂 

分 类 号：R734.2[医药卫生—肿瘤]