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Abstract：
The antitumor effect of norcantharidin (NCTD) has been widely reported. However, whether NCTD can inhibit cervical cancer remains unknown. In the present study, it was shown that NCTD inhibited the viability of cervical cancer cells and caused cell cycle arrest in a concentration‑dependent manner. Further analysis revealed that the NCTD‑induced reduction in cell viability could be reversed by the inhibitor of apoptosis z‑VAD‑FMK and by the inhibitor of endoplasmic reticulum (ER) stress, 4‑phenylbutyric acid (4‑PBA). Additionally, NCTD led to the accumulation of reactive oxygen species as well as a decrease in the mitochondrial membrane potential in cervical cancer cells, whereas 4‑PBA pre‑treatment attenuated these alterations. In addition, NCTD increased the expression of the apoptosis‑related proteins Bip, activating transcription factor (ATF) 4 and C/EBP homologous protein in a concentration‑dependent manner. Moreover, NCTD significantly increased the expression of the ER stress‑related signaling molecules protein kinase R‑like ER kinase, inositol‑requiring enzyme 1 and ATF6, but 4‑PBA abolished these effects. In vivo experiments showed that NCTD significantly inhibited the growth of subcutaneous tumors in mice. Additionally, the expression of ER stress‑related molecules and apoptosis‑related proteins increased significantly after NCTD treatment. In conclusion, NCTD induces apoptosis by activating ER stress and ultimately curtails the progression of cervical cancer.
摘要：
去甲斑驳素(NCTD)的抗肿瘤作用已被广泛报道。然而,NCTD是否能抑制宫颈癌尚不清楚.在本研究中,研究表明，NCTD抑制宫颈癌细胞的活力，并以浓度依赖性方式引起细胞周期停滞。进一步的分析表明，NCTD诱导的细胞活力降低可以通过凋亡抑制剂z-VAD-FMK和内质网（ER）应激抑制剂逆转，4-苯基丁酸（4-PBA）。此外,NCTD导致宫颈癌细胞中活性氧的积累以及线粒体膜电位的降低，而4-PBA预处理减弱了这些改变。此外,NCTD增加了凋亡相关蛋白Bip的表达，激活转录因子（ATF）4和C/EBP同源蛋白呈浓度依赖性。此外，NCTD显著增加ER应激相关信号分子蛋白激酶R样ER激酶的表达，需要肌醇的酶1和ATF6，但4-PBA消除了这些作用。体内实验表明，NCTD显著抑制小鼠皮下肿瘤的生长。此外,NCTD治疗后，ER应激相关分子和凋亡相关蛋白的表达显着增加。总之,NCTD通过激活ER应激诱导细胞凋亡并最终抑制宫颈癌的进展。
