Anti-cancer chemo-drugs can cause a rapid elevation of intracellular reactive oxygen species (ROS) levels. An imbalance in ROS production and elimination systems leads to cancer cell resistance to chemotherapy. This study aimed to evaluate the mechanism and effect of ROS on multidrug resistance in various human chemoresistant cancer cells by detecting the changes in the amount of ROS, the expression of ROS-related and glycolysis-related genes, and cell death. We found that ROS was decreased while oxidative phosphorylation was increased in chemoresistant cells. We verified that the chemoresistance of cancer cells was achieved in two ways. First, chemoresistant cells preferred oxidative phosphorylation instead of anaerobic glycolysis for energy generation, which increased ATPase activity and produced much more ATP to provide energy. Second, ROS-scavenging systems were enhanced in chemoresistant cancer cells, which in turn decreased ROS amount and thus inhibited chemo-induced cell death. Our in vitro and in vivo photodynamic therapy further demonstrated that elevated ROS production efficiently inhibited chemo-drug resistance and promoted chemoresistant cell death. Taken together, targeting ROS systems has a great potential to treat cancer patients with chemoresistance.

中文翻译：

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通过光动力疗法增强细胞内活性氧物质可有效促进耐化学性细胞死亡。

抗癌化疗药物可导致细胞内活性氧 (ROS) 水平快速升高。ROS产生和消除系统的不平衡导致癌细胞对化疗产生耐药性。本研究旨在通过检测 ROS 含量的变化、ROS 相关基因和糖酵解相关基因的表达以及细胞死亡情况来评估 ROS 对多种人类化学耐药癌细胞多药耐药的机制和影响。我们发现化学抗性细胞中 ROS 减少，而氧化磷酸化增加。我们验证了癌细胞的化学抗性是通过两种方式实现的。首先，化学抗性细胞更喜欢氧化磷酸化而不是厌氧糖酵解来产生能量，这增加了 ATP 酶活性并产生更多的 ATP 来提供能量。第二，化学抗性癌细胞中的 ROS 清除系统得到增强，这反过来又降低了 ROS 的数量，从而抑制了化学诱导的细胞死亡。我们的体外和体内光动力疗法进一步证明，升高的 ROS 产生有效地抑制了化学耐药性并促进了化学耐药性细胞死亡。总而言之，靶向 ROS 系统具有治疗具有化学抗性的癌症患者的巨大潜力。