Human
melanoma is a highly aggressive type of
cancer, causing significant mortalities despite the advances in treatment.
Carboplatin is a
cisplatin analog necessary for the treatment of various
cancers and can also be used to treat human
melanoma. We assessed the effects and mechanisms leading to inhibited proliferation and induced apoptosis of human
melanoma after
carboplatin therapy in vitro and in vivo. TREX1, cGAS/
STING, and apoptotic
protein expressions were determined through RT-qPCR and western blot assays. Cell proliferation was validated through MTT assays. The study used SK-MEL-1 and SK-HEP-1 tumor cell line inoculations along with
carboplatin in nude mice to validate the results. The TREX1 levels were down-regulated in human
melanoma cell lines. TREX1 overexpression-induced apoptosis and decreased proliferation in the human
melanoma cell lines. TREX1 overexpression also activated the cGAS/
STING pathway to induce apoptosis and decrease cell growth.
Carboplatin activated TREX1, induced apoptosis, and decreased proliferation in the human
melanoma cancerous cell lines. Finally,
carboplatin reduced the in-vivo
tumor size and weight. In conclusion, the study revealed that
carboplatin activated TREX1 and cGAS/
STING pathways to upregulate apoptosis. The work also provides in vitro and in vivo evidence to understand the effects of TREX overexpression on
tumor suppression. Targeting of TREX1/cGAS/
STING pathway could be an effective therapeutic alternative to human
melanoma.