Wu Yingchao, Pi Dajin, Chen Yiliu, Zuo Qian, Lin Lizhu, Ouyang Mingzi
School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, Guangdong, China.
MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China.
Evid Based Complement Alternat Med. 2022 Aug 22;2022:2357616. doi: 10.1155/2022/2357616. eCollection 2022.
Chemotherapy-related fatigue (CRF), one of the most severe adverse effects observed in cancer patients, has been theoretically related to oxidative stress, and antioxidant treatment might be one of the most valuable therapeutic approaches. However, there are still few effective pharmacological therapies. (YFSJ), a classical formula used to treat lung cancer as complementary and alternative medicine, have been proved to alleviate CRF of lung cancer patients in clinical practices. However, the underlying mechanisms have not been clarified. In this study, our data showed that YFSJ alleviated CRF presented as reversing the decline of swimming time and locomotor activity induced by cisplatin (DDP). Moreover, YFSJ significantly reduces the accidence of mitophagy and mitochondrial damage and reduces apoptosis in skeletal muscle tissues caused by DDP. It probably works by decreasing the oxidative stress, inhibiting the activation of the AMPK/mTOR pathway, decreasing protein expression levels of Beclin1 and other autophagy-related proteins, and attenuating the activation of Cytochrome c (cyto. C), Cleaved Caspase-9 (c-Casp 9), and other apoptosis-related proteins. Furthermore, YFSJ enhanced DDP sensitivity by specifically promoting oxidative stress and activating apoptosis and autophagy in the tumor tissues of mice. It was also found that YFSJ reduced the loss of body weight caused by DDP, reversed the ascent of serum concentrations of alanine aminotransferase (ALT), aminotransferase (AST), and creatinine (CREA), increased the spleen index, and prolonged the survival time of mice. Taken together, these results revealed that YFSJ could alleviate CRF by reducing mitophagy and apoptosis induced by oxidative stress in skeletal muscle; these results also displayed the effects of YFSJ on enhancing chemotherapy sensitivity, improving quality of life, and prolonging survival time in lung cancer mice received DDP chemotherapy.
化疗相关疲劳（CRF）是癌症患者中观察到的最严重的不良反应之一，理论上与氧化应激有关，抗氧化治疗可能是最有价值的治疗方法之一。然而，目前仍然很少有有效的药物治疗方法。益肺散结方（YFSJ）作为一种用于治疗肺癌的经典中药复方，已被证实在临床实践中可缓解肺癌患者的CRF。然而，其潜在机制尚未阐明。在本研究中，我们的数据表明，YFSJ可通过逆转顺铂（DDP）诱导的游泳时间和运动活性下降来减轻CRF。此外，YFSJ可显著降低骨骼肌组织中线粒体自噬和线粒体损伤的发生率，并减少DDP引起的细胞凋亡。其作用机制可能是通过降低氧化应激，抑制AMPK/mTOR通路的激活，降低Beclin1和其他自噬相关蛋白的表达水平，以及减弱细胞色素c（cyto. C）、裂解的半胱天冬酶-9（c-Casp 9）和其他凋亡相关蛋白的激活。此外，YFSJ通过特异性促进氧化应激和激活小鼠肿瘤组织中的细胞凋亡和自噬来增强DDP敏感性。还发现YFSJ可减轻DDP引起的体重减轻，逆转血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和肌酐（CREA）浓度的升高，增加脾脏指数，并延长小鼠的生存时间。综上所述，这些结果表明，YFSJ可通过减少氧化应激诱导的骨骼肌线粒体自噬和细胞凋亡来减轻CRF；这些结果还显示了YFSJ在接受DDP化疗的肺癌小鼠中增强化疗敏感性、改善生活质量和延长生存时间的作用。
