Abstract:

Objective　To investigate the effects of hyperbaric oxygen (HBO) on the proliferation and apoptosis of endometrial cancer (EC) cells, and to analyze the possible mechanism. Methods　From April 2022 to January 2023, the EC cell line RL95-2 was cultured in vitro and divided into a blank control group, an HBO group, a pathway activator group [100 μmol/L dimethylacetoylglycine (DMOG)], and an HBO + pathway activator group (HBO + 100 μmol/L DMOG). The MTT assay and flow cytometry were used to detect the cell proliferation and apoptosis. Western blot was used to detect the expressions of cell proliferation associated nuclear antigen (Ki-67), Bcl-2, Bax, and hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway related proteins. One-way analysis of variance was used for the statistical analysis. Results　The proliferation inhibition rates of the blank control group, the HBO group, the pathway activator group, and the HBO + pathway activator group were 0, (33.85±5.07)%, (-4.89±0.73)%, and (9.82±1.47)%, respectively, with a statistical difference between the 4 groups (F=244.919,P<0.001). The apoptosis rates of the four groups were (16.79±2.51)%, (34.65±5.18)%, (5.73±0.86)%, and (9.69±1.45)%, respectively, with a statistical difference (F=109.342; P<0.001). The proliferation inhibition rate, apoptosis rate, and Bax protein in the HBO group were higher than those in the blank control group, the HIF-1α/VEGF pathway protein was lower (all P<0.05). The proliferation inhibition rate, apoptosis rate, and Bax protein in the pathway activator group were lower than those in the blank control group, while the HIF-1α/VEGF pathway protein was higher (all P<0.05). Conclusions　HBO can inhibit EC cell proliferation and induce apoptosis. Its mechanism is related to the inhibition of the HIF-1α/VEGF pathway.

Key words:

Hyperbaric oxygen, Endometrial cancer, Proliferation, Apoptosis, Hypoxia inducible factor-1α, Vascular endothelial growth factor pathway

摘要：

目的　探讨高压氧（HBO）对子宫内膜癌（EC）细胞增殖、凋亡的影响及其可能机制。方法　2022年4月至2023年1月，体外培养RL95-2（EC细胞系细胞株），分为4组。空白对照组：只含RL95-2细胞；HBO组：采用氧帐持续流量供氧法处理RL95-2细胞；通路激活剂组：采用100 μmol/L 缺氧诱导因子1α（HIF-1α）激活剂二甲基乙二酰基甘氨酸（DMOG）处理RL95-2细胞；HBO+通路激活剂组：用100 μmol/L DMOG和HBO处理RL95-2细胞。使用四甲基偶氮唑蓝（MTT）法、流式细胞仪分别检测各组细胞增殖和凋亡；免疫印迹法检测增殖细胞核抗原-67（Ki-67）、B细胞淋巴瘤因子2蛋白（Bcl-2）、BCL2关联X蛋白（Bax）及HIF-1α/血管内皮生长因子（VEGF）通路相关蛋白表达。统计学方法采用单因素方差分析。结果　空白对照组、HBO组、通路激活剂组、HBO+通路激活剂组增殖抑制率分别为0、（33.85±5.07）%、（-4.89±0.73）%、（9.82±1.47）%，4组增殖抑制率比较，差异有统计学意义（F=244.919，P<0.001）；4组细胞凋亡率分别为（16.79±2.51）%、（34.65±5.18）%、（5.73±0.86）%、（9.69±1.45）%，差异有统计学意义（F=109.342，P<0.001）。与空白对照组比较：HBO组细胞增殖抑制率、凋亡率、Bax蛋白均高于空白对照组，HIF-1α/VEGF通路蛋白低于空白对照组（均P<0.05）；通路激活剂组细胞增殖抑制率、凋亡率、Bax蛋白均低于空白对照组，HIF-1α/VEGF通路蛋白高于空白对照组（均P<0.05）。结论　HBO可抑制EC细胞增殖并诱导细胞凋亡，其作用机制与抑制HIF-1α/VEGF通路有关。

关键词:

高压氧, 子宫内膜癌, 增殖, 凋亡, 缺氧诱导因子1α, 血管内皮生长因子通路