Triptolide avoids cisplatin resistance and induces apoptosis via the reactive oxygen species/nuclear factor-κB pathway in SKOV3PT platinum-resistant human ovarian cancer cells

An acquired resistance to platinum‑based drugs has emerged as a significant impediment to effective ovarian cancer therapy. The present study explored the anticancer mechanisms of triptolide (TPL) in SKOV3PT platinum‑resistant human ovarian cancer cells and observed that TPL activated caspase 3 and induced the dose‑dependent apoptosis of the SKOV3PT cells. Furthermore, TPL inhibited complex I of the mitochondrial respiratory chain (MRC) followed by an increase of reactive oxygen species (ROS), which further inhibited nuclear factor (NF)‑κB activation and resulted in the downregulation of anti‑apoptotic proteins, Bcl‑2 and X‑linked inhibitor of apoptosis protein (XIAP). Notably, the pre‑treatment with N‑acetyl‑L‑cysteine (NAC) abolished the TPL‑induced ROS generation, NF‑κB inhibition and cell apoptosis, but did not affect the inhibitory effect of TPL on complex I activity. These results suggested that TPL negatively regulated the NF‑κB pathway through mitochondria‑derived ROS accumulation, promoting the apoptosis of the SKOV3PT cells. Furthermore, TPL synergistically enhanced the cytotoxicity of cisplatin against platinum‑resistant ovarian cancer cells. Collectively, these findings suggest that TPL is able to overcome chemoresistance and that it may be an effective treatment for platinum‑resistant ovarian cancer, either alone or as an adjuvant therapy.