RESUMEN
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 concentrationdependent manner. Further analysis revealed that the NCTDinduced reduction in cell viability could be reversed by the inhibitor of apoptosis zVADFMK and by the inhibitor of endoplasmic reticulum (ER) stress, 4phenylbutyric acid (4PBA). 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 4PBA pretreatment attenuated these alterations. In addition, NCTD increased the expression of the apoptosisrelated proteins Bip, activating transcription factor (ATF) 4 and C/EBP homologous protein in a concentrationdependent manner. Moreover, NCTD significantly increased the expression of the ER stressrelated signaling molecules protein kinase Rlike ER kinase, inositolrequiring enzyme 1 and ATF6, but 4PBA abolished these effects. In vivo experiments showed that NCTD significantly inhibited the growth of subcutaneous tumors in mice. Additionally, the expression of ER stressrelated molecules and apoptosisrelated proteins increased significantly after NCTD treatment. In conclusion, NCTD induces apoptosis by activating ER stress and ultimately curtails the progression of cervical cancer.
