Resistant mechanisms of cisplatin in human lung adenocarcinoma cell line A549DDP
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To study the resistant mechanisms of cisplatin in human lung adenocarcinoma cell line A549DDP. A549DDP cells was established by stepwise increasing concentration of cisplatin (CDDP) in medium. Interstrand cross-linked DNA (ICL) was measured by ethidium bromide fluorescence assay. The intracellular and intranuclear accumulation of cisplatin was measured by atomic absorption spectrometry. The removal of GS-X was determined by FCM and fluorescence microscopy. Results: The A549DDP cell line was 8.9-fold resistance relative to the parental A549 cell line. The formation of ICL in A549 was 6.28 times higher than that in A549DDP cells. The intracellular and intranuclear accumulation of cisplatin in A549 cells was 5.9 times and 4.1 times higher than that in A549DDP cells, respectively. The ability of GS-X pump pumped GS-X complex (GS-Pt) in A549DDP cells was higher than that in A549. The repair rate in A549DDP cells was 2 times higher than that in A549. Conclusions: Decreased accumulation and increased export of cisplatin might be the main mechanism of cisplatin resistant A549DDP cells while the enhanced repair capacity of DNA may play a role in CDDP resistance.
Key wordsResistance mechanism Human A549 Cisplatin Interstrand cross-link Accumulation DNA repair capacity
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