Cancer chemotherapy drugs are widely criticized for their serious side effects and low cure rate. Therefore, adjuvant
therapy as a combination with
chemotherapy administration is being accepted by many patients. However, unclear drug targets and mechanisms limit the application of adjuvant treatment. In this study, we confirmed TMEM16A is a key drug target for
lung adenocarcinoma, and
narirutin is an effective anti-
lung adenocarcinoma natural product. Virtual screening and fluorescence experiments confirmed that
narirutin inhibits the molecular target TMEM16A, which is specific high-expression in
lung adenocarcinoma. Molecular dynamics simulations and electrophysiological experiments revealed the precise molecular mechanism of
narirutin regulating TMEM16A. The anticancer effect of
narirutin and its synergistic effect on
cisplatin were explored by cell proliferation, migration, and apoptosis assays. The signaling pathways regulated by
narirutin were analyzed by western blot.
Tumor xenograft mice experiments demonstrated the synergistic anticancer effect of
narirutin and
cisplatin, and the side effects of high concentrations of
cisplatin were almost eliminated. Pharmacokinetic experiments showed the biological safety of
narirutin is satisfactory in vivo. Based on the significant anticancer effect and high biosafety,
naringin has great potential as a functional food in the adjuvant treatment of
lung cancer.