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Effects of hyperbaric oxygen on enhancing the drug sensitivity of gemcitabine-resistant human lung cancer A549 cell lines to gemcitabine

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Author:
No author available
Journal Title:
Chinese Journal of Health Management
Issue:
4
DOI:
10.3760/cma.j.cn311847-20210715-00207
Key Word:
高压氧;吉西他滨;人肺癌A549细胞;耐药性;Hyperbaric oxygen;Gemcitabine;Human lung cancer A549 cells;Drug resistance

Abstract: Objective:To study the reversal effect and the mechanism of hyperbaric oxygen(HBO)on gemcitabine(Gem)-resistance of human lung cancer A549 cell lines.Methods:The A549 cell lines were exposed to stepwise escalating concentration of Gem in vitro until the Gem-resistant A549(A549/Gem)cell lines were developed. The CCK-8 and flow cytometry were used to detect the effect of HBO on the proliferation and apoptosis of A549/GEM cells,respectively,and western blot was used to detect the expression levels of apoptosis proteins,drug-resistant proteins,and the chromobox protein homolog 6(CBX6)in A549/GEM cells.Results:Compared with those in the control,HBO,and Gem groups,the proliferation of A549/GEM cells in the HBO + GEM group was significantly inhibited( P<0.01). The apoptosis ratio in the HBO + GEM group was 32.4%,which was much higher than those in the control(1.08%),HBO(5.42%),and GEM groups(9.28%),with statistically significant differences( P<0.01). Western blot results showed that,in the HBO + GEM group,the expression levels of apoptosis proteins,such as Bcl-2,significantly decreased,and the expression levels of Bad and Caspase-3 significantly increased,and all the differences were statistically significant( P<0.01). In the HBO + GEM group,the expression levels of drug-resistant P-glycoprotein(P-gp)and MRP-related protein(MRP)in the A549/GEM cells significantly decreased,and the differences were statistically significant( P<0.01). The expression level of CBX6 in the HBO + GEM group was significantly up-regulated. Conclusion:The combination of HBO and Gem can significantly reduce the resistance of A549/GEM cells to Gem,and its main mechanism is to up-regulate the expression level of channel proteins and down-regulate the expression level of drug-resistant proteins,thus regulating the expressions of apoptosis-related proteins and promoting the apoptosis of A549/GEM cells.

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