Abstract:

Objective To investigate whether pristimerin（PRIS）enhances the anti⁃cancer effect of cispla⁃ tin and its underlying mechanism. Methods Patient ⁃derived lung cancer cells were established by conditional reprogramming technology. MTS was used to detect the proliferation activity. Calcein ⁃AM/PI double staining was used to detect the cell state. Transwell assay was used to detect the migration and invasion ability of cells. Annexin V⁃APC flow cytometry was used to detect cell apoptosis. DCFH⁃DA staining was used to measure the ROS levels of the cells. JC ⁃ 1 staining and DiOC6 staining were used to determine the mitochondrial membrane potential qualitatively and quantitatively. qRT⁃PCR and Western Blot were used to detect the mRNA and protein expression. Results As compared with a monotherapy，pristimerin combined with cisplatin significantly inhibited the viability， migration and invasion of the cells（P < 0.01）. Besides，the combination of the two drugs significantly improved the intracellular levels of ROS（P < 0.01）while reduced cell mitochondrial membrane potential（P < 0.01）and inhibited the expressions of NRF2 and HO ⁃1，thus increasing apoptosis（P < 0.01）. Conclusions Pristimerin may enhance the anti⁃cancer ability of cisplatin，whose mechanism may be involved in inhibiting the expressions of NRF2 and HO⁃1 in the KEAP1⁃NRF2/HO⁃1 signaling pathway.

Key words:

pristimerin, cisplatin, conditionally reprogrammed lung cancer cells, oxidative stress, KEAP1?NRF2/HO?1 signaling pathway