Abstract
Cervical cancer remains a significant global health burden, particularly in developing countries, despite advances in screening and prevention. Novel therapeutic strategies are urgently needed to improve outcomes for patients with advanced or metastatic disease. Triptolide (TL), a key component of the Chinese herb Tripterygium wilfordii, has shown potent anticancer effects in various malignancies. In this study, we investigated the anticancer effects of TL on cervical cancer cells in vitro and in vivo, focusing on its ability to induce immunogenic cell death (ICD). TL exhibited potent cytotoxicity, inhibited proliferation, induced apoptosis, and suppressed tumor growth in cervical cancer models. Mechanistically, TL induced ICD in cervical cancer cells, as evidenced by the calreticulin (CRT) exposure on the cell surface and the release of HMGB1 and ATP. TL-induced CRT exposure was mediated by endoplasmic reticulum (ER) stress, as demonstrated by the upregulation of ATF3 and the activation of oxidative stress and immune pathways. Oral administration of TL significantly inhibited tumor growth in a cervical cancer xenograft model, without overt toxicities. These findings highlight the potential of TL as a novel immunotherapeutic agent for cervical cancer and warrant further investigation into its clinical translation. The combination of TL with immune checkpoint inhibitors or other immunotherapies may provide a promising strategy to enhance the efficacy of cervical cancer treatment while minimizing adverse effects.