OBJECTIVE Intermittent hypoxia, a significant feature of obstructive sleep apnea, has pro-tumorigenic effects. Here, we investigated the effect of sodium tanshinone IIA sulfonate on oxidative stress and apoptosis in a mouse model of Lewis lung carcinoma with intermittent hypoxia. METHODS Mice were randomly assigned to normoxia (control), normoxia plus sodium tanshinone IIA sulfonate (control + sodium tanshinone IIA sulfonate), intermittent hypoxia, and intermittent hypoxia + sodium tanshinone IIA sulfonate groups. Intermittent hypoxia administration lasted 5 weeks in the intermittent hypoxia groups. Lewis lung carcinoma cells were injected into the right flank of each mouse after 1 week of intermittent hypoxia exposure. Sodium tanshinone IIA sulfonate was injected intraperitoneally in the control + sodium tanshinone IIA sulfonate and intermittent hypoxia + sodium tanshinone IIA sulfonate groups. Tumor oxidative stress was evaluated by detection of malondialdehyde and superoxide dismutase. The apoptosis of tumor cells was evaluated by the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay as well as by Western blot analysis of B-cell lymphoma 2-associated X protein and cleaved caspase-3 expression. Additionally, the expression of hypoxia-induced factor-1α, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa B was also evaluated by Western blot. RESULTS Compared with the control group, the intermittent hypoxia treatment significantly increased Lewis lung carcinoma tumor growth and oxidative stress (serum malondialdehyde) but decreased serum levels of SOD and pro-apoptotic markers (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, B-cell lymphoma 2-associated X protein, and cleaved caspase-3). These changes were significantly attenuated by intraperitoneal injection of sodium tanshinone IIA sulfonate. Lower nuclear factor erythroid 2-related factor 2 and higher nuclear factor kappa B levels in the intermittent hypoxia group were clearly reversed by sodium tanshinone IIA sulfonate treatment. In addition, sodium tanshinone IIA sulfonate administration decreased the high expression of hypoxia-induced factor-1α induced by intermittent hypoxia. CONCLUSION Intermittent hypoxia treatment resulted in high oxidative stress and low apoptosis in Lewis lung carcinoma-implanted mice, which could be attenuated by sodium tanshinone IIA sulfonate administration possibly through a mechanism mediated by the nuclear factor erythroid 2-related factor 2/nuclear factor kappa B signaling pathway.

中文翻译：

---

丹参酮IIA磺酸钠可减轻间歇性缺氧小鼠模型中的肿瘤氧化应激并促进细胞凋亡。

目的间歇性缺氧是阻塞性睡眠呼吸暂停的重要特征，具有促肿瘤作用。在这里，我们调查了丹参酮IIA磺酸钠对间歇性缺氧的Lewis肺癌小鼠模型中氧化应激和细胞凋亡的影响。方法将小鼠随机分为正常氧（正常），正常氧加丹参酮IIA磺酸钠（对照组+丹参酮IIA磺酸钠），间歇性缺氧和间歇性缺氧+丹参酮IIA磺酸钠组。在间歇性缺氧组中，间歇性缺氧给药持续了5周。在间歇性缺氧暴露1周后，将Lewis肺癌细胞注射到每只小鼠的右侧腹。在对照组+丹参酮IIA磺酸钠和间歇性缺氧+丹参酮IIA磺酸钠组中腹膜内注射丹参酮IIA磺酸钠。通过检测丙二醛和超氧化物歧化酶评估肿瘤的氧化应激。通过末端脱氧核苷酸转移酶dUTP缺口末端标记测定以及通过B细胞淋巴瘤2相关X蛋白和裂解的caspase-3表达的蛋白质印迹分析来评估肿瘤细胞的凋亡。另外，还通过Western印迹评估了缺氧诱导的因子-1α，核因子类红细胞2相关因子2和核因子κB的表达。结果与对照组相比，间歇性低氧治疗可显着增加Lewis肺癌的肿瘤生长和氧化应激（血清丙二醛），但降低血清SOD和促凋亡标记物的水平（末端脱氧核苷酸转移酶dUTP缺口末端标记染色，B细胞淋巴瘤2相关X蛋白，并切割了caspase-3）。腹膜内注射丹参酮IIA磺酸钠可大大减轻这些变化。丹参酮IIA磺酸钠治疗可明显逆转间歇性缺氧组中较低的核因子类胡萝卜素2相关因子2和较高的核因子kappa B水平。此外，丹参酮IIA磺酸钠的给药降低了间歇性缺氧诱导的缺氧诱导因子-1α的高表达。