TMEM16A plays critical roles in physiological process and may serve as drug targets for diverse diseases. Recently, TMEM16A has started to be regarded as potential primary lung adenocarcinoma targets. Here, we identified that arctigenin, a natural compound, is a novel TMEM16A inhibitor, and it can suppress lung adenocarcinoma growth through inhibiting TMEM16A both in vitro and in vivo. Our data also showed that the IC₅₀ of actigenin to TMEM16A whole-cell current was 19.29 ± 4.69 μM, and the putative binding sites of arctigenin in TMEM16A were R515 and R535. Arctigenin concentration-dependently inhibited the proliferation and migration of LA795, however, the inhibition effect can be abolished by knockdown of the endogenous TMEM16A with shRNA. Further, we injected arctigenin on xenograft mouse model which exhibited significant antitumor activity with no adverse effect. At last, western blotting results showed the mechanism of arctigenin inhibiting lung adenocarcinoma was through inhibiting MAPK pathway. In summary, TMEM16A is a novel drug target for lung adenocarcinoma treatment. Arctigenin can be used as a lead compound for the development of lung adenocarcinoma therapy drugs.

TMEM16A在生理过程中起着关键作用，并且可以作为多种疾病的药物靶标。最近，TMEM16A已开始被视为潜在的原发性肺腺癌靶标。在这里，我们确定了牛蒡苷元，天然化合物，是一种新颖的TMEM16A抑制剂，并且它可以通过两个抑制TMEM16A抑制肺腺癌生长的体外和体内。我们的数据还显示，IC ₅₀肌动蛋白原对TMEM16A全细胞电流的作用为19.29±4.69μM，而推定的arctigenin在TMEM16A中的结合位点为R515和R535。Arctigenin浓度依赖性地抑制LA795的增殖和迁移，但是，通过用shRNA敲除内源性TMEM16A可以消除抑制作用。此外，我们在异种移植小鼠模型上注射了Arctigenin，该模型表现出显着的抗肿瘤活性且无不良影响。最后，Western blotting结果显示arcgeninin抑制肺腺癌的机制是通过抑制MAPK途径。总之，TMEM16A是治疗肺腺癌的新型药物靶标。Arctigenin可用作开发肺腺癌治疗药物的先导化合物。