Triptolide Enhances Chemotherapeutic Accumulation Through P-Gp Inhibition in Cisplatin-Resistant HNE1/DDP Nasopharyngeal Cancer Cells

Background: We have previously shown that triptolide (TPL) could synergize with cisplatin (DDP) in drug-resistant nasopharyngeal cancer cells (NPC). However, the underlying mechanism remains elusive. Therefore, we hypothesized that TPL could inhibit P-glycoprotein (P-gp) expression, reduce the chemotherapeutic agent efflux from tumor cells and increase their drug content, then by increasing drug efficiency against the tumor cells. So the study was performanced to elucidate the mechanism of triptolide (TPL) sensitization with chemotherapeutics in drug-resistant nasopharyngeal cancer cells. Methods and Results:Cell viability was analyzed by MTT. The apoptosis and intracellular concentration of doxorubicin/rhodanmine123 were determined by flow cytometry. The expression of P-gp, MRP1, Caspse-3, CAP1, and CAP2 were measured by western blot. The ATP level was examined by Cell Titer-Glo Luminescent Cell Viability Assay kit. The results showed that TPL inhibited cell viability, increased apoptosis, and intracellular doxorubicin accumulation. Furthermore, TPL inhibited the rhodanmine123 efflux, reduced the ATP level and the expression of P-gp, MRP1, and CAP1, while it increased the expression of CAP2 and Caspase-3. Conclusions:The results of this study confirm the role of TPL in restoring the sensitivity of cancer cells to chemotherapeutics by down regulating P-gp expression and function in drug-resistant nasopharyngeal cancer cells.

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