Malignant melanoma is a fatal disease with an increasing incidence rate all around the world. The standard therapy for melanoma is cancer radical surgery followed by chemotherapy and radiotherapy, but the effect is far from satisfaction and patients with these treatments still succumb to melanoma which appeals to a safer and more effective therapy. Artemisinin and its derivatives (termed Arts) are safe and effective anti-malarial drugs used in clinics for decades. Recently, Arts have been reported to present a wide range of bioactivities, including the anti-cancer effect. However, there is no information available regarding the effect of Arts on melanoma recurrence and metastasis after tumor excision.

In the present study, we investigated the effect of Arts on melanoma recurrence and metastasis after tumor excision and its underlying mechanism. Our results showed that the application of Arts after tumor excision blocked the melanoma recurrence and metastasis and extended the life expectancy of a host animal. RNA sequencing from both tissue and cell line samples identified several proteins, including c-KIT, as critical biomarkers in melanoma recurrence and metastasis regulated by Arts. Further mechanism studies involving transfection of overexpression plasmids and CRISPR-Cas9 knockout experiments were carried out, which confirmed the effect of Arts on downregulating c-KIT and its downstream signaling targets PI3K/Akt and some EMT (Epithelial-Mesenchymal Transitions) biomarkers. These data suggested that Arts suppressed melanoma recurrence and metastasis after radical surgery by inhibiting the c-KIT/PI3K/AKT signaling pathway.