Sodium cantharidinate (SC) has demonstrated efficacy in treating lung cancer in China, yet its effects in cervical cancer (CC)—a major cause of female reproductive cancer mortality—remain largely unexplored. This study investigates SC’s anti-cancer activity in CC and explores the molecular mechanisms involved. DDP-resistant Caski-1 and ME180 cervical cancer cell lines were established and treated with SC to assess its impact on cell proliferation. Potential molecular targets of SC were predicted using bioinformatics analyses. Associations between PTPN1 expression and clinical features, including tumor stage, lymph node metastasis, and tumor differentiation, were evaluated. Functional studies included overexpressing PTPN1 in CC cells followed by treatment with SC and cisplatin. Additionally, the influence of SC on PI3K/AKT signaling and its effects on tumor growth and cisplatin resistance were assessed in vivo. SC treatment increased the responsiveness of Caski-1 and ME180 cells to cisplatin, augmenting its inhibitory effect on cell growth. Bioinformatic predictions suggested PTPN1 as a key SC target. Clinically, higher PTPN1 levels were correlated with advanced disease stage, lymph node involvement, and poor differentiation. SC suppressed PTPN1 expression, and PTPN1 overexpression reduced SC’s anti-proliferative effects. Mechanistically, PTPN1 activated the PI3K/AKT pathway, which was inhibited by SC. In animal models, SC limited tumor growth and reversed cisplatin resistance. SC sensitizes cervical cancer cells to cisplatin by downregulating PTPN1 and inhibiting the PI3K/AKT pathway, highlighting its potential as a complementary therapeutic strategy.
