Henan Key Laboratory of Ion-Beam Bioengineering, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450001, China.
College of Nursing and Health, Zhengzhou University, Zhengzhou 450001, China.
Molecules. 2023 Feb 2;28(3):1461. doi: 10.3390/molecules28031461.
Esophageal cancer is a highly aggressive malignancy with a low response to standard anti-cancer therapies. There is an unmet need to develop new therapeutic strategies to improve the clinical outcomes of current treatments. Cold atmospheric plasma (CAP) is a promising approach for cancer treatment, and has displayed anticancer efficacy in multiple preclinical models. Recent studies have shown that the efficacy of CAP is positively correlated with intracellular reactive oxygen species (ROS) levels. This suggests that aggressively increasing intracellular ROS levels has the potential to further improve CAP-mediated anticancer efficacy. Glutamine plays an important role in cellular ROS scavenging after being converted to glutathione (GSH, a well-described antioxidant) under physiological conditions, so reducing intracellular glutamine levels seems to be a promising strategy. To test this hypothesis, we treated esophageal cancer cells with CAP while controlling the supply of glutamine. The results showed that glutamine did affect the anticancer effect of CAP, and the combination of CAP stimulation and glutamine deprivation significantly inhibited the proliferation of esophageal cancer cells compared to the control group ( < 0.05). Furthermore, flow cytometric analysis documented a significant increase in more than 10% in apoptosis and necrosis of esophageal cancer cells after this synergistic treatment compared to the control group ( < 0.05). Thus, these results provide the first direct evidence that the biological function of CAP can be modulated by glutamine levels and that combined CAP stimulation and glutamine deprivation represent a promising strategy for the future treatment of esophageal cancer.
食管癌是一种侵袭性很强的恶性肿瘤，对标准抗癌疗法的反应率较低。因此，需要开发新的治疗策略，以改善当前治疗的临床效果。冷等离体（CAP）是一种很有前途的癌症治疗方法，在多种临床前模型中已显示出抗癌疗效。最近的研究表明，CAP 的疗效与细胞内活性氧（ROS）水平呈正相关。这表明，积极增加细胞内 ROS 水平有潜力进一步提高 CAP 介导的抗癌疗效。在生理条件下，谷氨酰胺转化为谷胱甘肽（GSH，一种众所周知的抗氧化剂）后，在细胞内 ROS 清除中起着重要作用，因此降低细胞内谷氨酰胺水平似乎是一种很有前途的策略。为了验证这一假设，我们在 CAP 处理的同时控制谷氨酰胺的供应，用 CAP 处理食管癌细胞。结果表明，谷氨酰胺确实会影响 CAP 的抗癌效果，与对照组相比，CAP 刺激和谷氨酰胺剥夺的联合作用显著抑制了食管癌细胞的增殖（<0.05）。此外，流式细胞术分析显示，与对照组相比，这种协同治疗后食管癌细胞的凋亡和坏死率显著增加了 10%以上（<0.05）。因此，这些结果首次直接证明，CAP 的生物学功能可以通过谷氨酰胺水平来调节，并且 CAP 刺激和谷氨酰胺剥夺的联合作用代表了未来治疗食管癌的一种很有前途的策略。
