JI-CJ002 and Dabrafenib Combination Enhances Antitumor Activity in Melanoma Associated With the Downregulation of B7-H3.

Melanoma is the most lethal form of skin cancer, with a significantly poor prognosis after metastasis. The BRAF inhibitor dabrafenib increases response rates and overall survival (OS) in advanced-stage melanoma; however, most patients develop resistance rapidly, highlighting the need for improved combination regimens. This study investigated the therapeutic efficacy of JI-CJ002, an herbal extract consisting of Angelica gigas, Aconitum carmichaeli, and Zingiber officinale blended in a 2:1:3 (w/w) ratio, and assessed the combined antineoplastic effects of JI-CJ002 with dabrafenib in melanoma. JI-CJ002 suppressed epithelial-mesenchymal transition (EMT), invasion, and melanin synthesis, and these effects were maintained in combination with dabrafenib. The combination treatment was associated with reduced B7-H3 expression, along with inhibition of signaling pathways implicated in melanoma progression, including JAK2/STAT3, PI3K/AKT/mTOR, and NF-κB. Efficacy of the combination regimen was further evaluated in an A375 xenograft murine model. In vivo studies demonstrated that combination therapy reduced tumor volume without causing systemic toxicity, accompanied by decreased proliferation markers (PCNA and Ki-67), increased apoptotic marker (cleaved caspase-3), and decreased B7-H3 expression in tumor tissues. These results suggest that JI-CJ002 may enhance the antitumor activity of dabrafenib, accompanied by modulation of oncogenic pathways.