Combined effects of low-dose gambogic acid and NaI131 in drug-resistant non-small cell lung cancer cells

Abstract

Radioactive seed brachytherapy is a method for treating drug-resistant, late-stage non-small cell lung cancer (NSCLC). To elucidate the mechanism of low-dose gambogic acid (GA) and NaI131 in drug-resistant NSCLC cells, the human NSCLC A549 cell line and the drug-resistant A549/cisplatin (DDP) and A549/Taxol cell lines were treated with NaI131, low-dose GA or a combination of both in the present study; the control group of each cell line was treated with phosphate-buffered saline (PBS). Following treatment, cell proliferation, apoptosis and cell cycle analysis was performed. Apoptosis-related proteins, namely CDK1, cyclin B, mutant p53 (mtp53), heat shock protein 90 (HSP90), Bax and Bcl-2, and P-glycoprotein 1 (P-gp), which is known to confer resistance to chemotherapy, were detected using western blotting and immunofluorescence analysis. mRNA levels of p53 and HSP90 were measured using reverse transcription-quantitative PCR. Compared with the PBS control group, the A549, A549/DDP and A549/Taxol cells treated with NaI131, GA or a combination of the drugs exhibited G2/M arrest and increased percentages of total apoptotic cells, as well as significantly decreased protein levels of CDK1, cyclin B, mtp53, HSP90, Bcl-2 and P-gp, increased protein levels of Bax and decreased mRNA levels of p53 and HSP90. The changes in the combination group were the most evident and were significantly different from the other groups (P<0.001). In conclusion, low-dose GA may be a potential radionuclide sensitizer.