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Hyperbaric oxygen combined with doxorubicin on the proliferation and apoptosis of human gastric cancer MKN45 cells

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Author:
No author available
Journal Title:
Chinese Journal of Health Management
Issue:
6
DOI:
10.3760/cma.j.cn311847-20210727-00216
Key Word:
高压氧;多柔比星;胃癌;MKN45细胞;细胞凋亡;Hyperbaric oxygen;Doxorubicin;Gastric carcinoma;Human gastric cancer MKN45 cells;Cell apoptosis

Abstract´╝Ü Objective:To explore the effect of hyperbaric oxygen(HBO)combined with doxorubicin(DOX)on the proliferation and apoptosis of human gastric cancer MKN45 cell line,the poorly differentiated adenocarcinoma cells,and its associated mechanism.Methods:After culturing human gastric cancer MKN45 cells in vitro,the cells were divided into four groups according to the experimental design:control group,DOX group,HBO group,and HBO+DOX group. The control group was given DMSO,and the DOX group was given DOX solution with a final concentration of 2 mg/L. The HBO group was exposed in the hyperbaric oxygen chamber(0.25 MPa)for 90 min,while the HBO+DOX group was given 2 mg/L of DOX after being exposed in a hyperbaric oxygen chamber for 90 min. The CCK-8 method was used to detect the inhibitory effect of HBO+DOX treatment on the proliferation of gastric cancer MKN45 cells;the flow cytometry was used to detect the apoptosis rate of gastric cancer MKN45 cells;and the western blotting was used to detect the expression levels of apoptosis proteins and JNK/STAT3 signaling pathway related proteins in gastric cancer MKN45 cells.Results:The survival rate of MKN45 cells in the HBO+DOX group was significantly lower than those in the control group,the HBO group( P<0.01),and in the PTX group( P<0.05). The apoptosis rate of MKN45 cells in the HBO+DOX group was significantly higher than those in the control group,the HBO group( P<0.01),and the PTX group( P<0.05). Compared with the control group and the HBO group,the expression levels of Bad,caspase-3,and PARP protein in MKN45 cells in the DOX group and the HBO+DOX group were significantly increased,while the expression levels of Bcl-2 protein were significantly decreased( P<0.01). PARP protein expression level in the DOX group was significantly lower than that in the HBO+DOX group( P<0.05). Compared with the control group and the HBO group,p-JNK protein expression levels in MKN45 cells in the DOX group and the HBO+DOX group decreased significantly,and the p-JNK protein expression level in the HBO+DOX group was lower than that in the DOX group( P<0.05 or P<0.01). Compared with the control group,the expression levels of p-STAT3 in MKN45 cells in the DOX group and the HBO+DOX group were significantly increased( P<0.05). Compared with the control group,HBO group,and DOX group,the drug resistance-related P-gp protein in MKN45 cells in the HBO+DOX group decreased significantly( P<0.01). Conclusion:HBO treatment can enhance the ability of DOX in inhibiting the proliferation and promoting the apoptosis of human gastric cancer MKN45 cells,and its mechanism may be realized by regulating the JNK/STAT3 signaling pathway in MKN45 cells.

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