SMAD3 and melanoma: In mouse melanoma and lung cancer models as well as in vitro studies, it was found that the synergistic use of AA with naringenin could inhibit Smad3-mediated MMP2 transcription, increase TIMP, and enhance Smad7, thereby inhibiting TGF-β/Smad3 signaling, and finally inhibit MMP2 to achieve the antitumor effect.