ABSTRACT
Paclitaxel (or Taxol®) is a first-line chemotherapeutic drug for the treatment of non-small cell lung cancer; however, resistance to the drug is an important factor, which influences the outcome of chemotherapy. The present study aimed to investigate the role of triptolide (TPL) in reversing Taxolresistant human lung adenocarcinoma and to elucidate the underlying molecular mechanism of resistance reversal mediated by TPL. It was hypothesized that this experimental approach would assist in solving the problem of chemotherapeutic resistance in nonsmall cell lung cancer, thereby improving the clinical outcomes. The human Taxolresistant lung adenocarcinoma cell line, A549/Taxol, was established. The resistance index of the cell line was calculated, according to the half maximal inhibitory concentration (IC50) of A549/Taxol IC50 of A549, to be 51.87. The levels of apoptosis and the cell cycle in the A549/Taxol cell line were assessed to confirm the effects of TPL at three different concentrations (0.03, 0.3 and 3 µmol/l) and treatment durations (2, 4, 6 and 12 h) by flow cytometric analysis, and the inhibition of the NFκB signaling pathway and the expression of NFκBregulated drugresistant proteins were determined by immunofluorescence and western blotting, respectively. The administration of TPL promoted cell apoptosis in the A549/Taxol lung adenocarcinoma Taxolresistant cell line and also promoted cell cycle regulation. The drug was also able to elicit a reversal of the drug resistance. TPL inhibited the nuclear factorκB (NFκB) signaling pathway and the expression of NFκBregulated drugresistant genes, including those for FLICElike inhibitory protein, Xlinked inhibitor of apoptosis protein, Bcl2, BclxL and cyclooxygenase2. TPL exerted a marked drugresistancereversal effect on human lung adenocarcinoma Taxol resistance, and the effect was revealed to be dose and timedependent. In conclusion, TPL exerted its role in the process of resistance reversal by inhibiting the NFκB signaling pathway, and the transcription and expression of NF-κB-regulated drug-resistant genes.