CP‐31398 inhibits the progression of cervical cancer through reversing the epithelial mesenchymal transition via the downregulation of PAX2s

• Published in: Journal of cellular physiology 2019-03, Vol.234 (3), p.2929-2942
• Main Authors: Liu, Ling, Yu, Tan‐Tan, Ren, Chen‐Chen, Yang, Li, Cui, Shi‐Hong, Zhang, Xiao‐An
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; cervical cancer (CC) cell; CP‐31398; Disease Progression; epithelial mesenchymal transition (EMT); Epithelial-Mesenchymal Transition - drug effects; Female; Gene Expression Regulation, Neoplastic - drug effects; Heterografts; Humans; Mice; paired box 2 (PAX2); PAX2 Transcription Factor - genetics; Pyrimidines - pharmacology; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.27109

CP‐31398, a styrylquinazoline, emerges from a screen for therapeutic agents that restore the wild‐type DNA‐binding conformation of mutant p53 to suppress tumors in vivo, but its effects on cervical cancer (CC) remain unknown. Hence, this study aimed to explore the effects CP‐31398 has on the CC cells and to investigate whether it is associated with paired box 2 (PAX2) expression. CC cells were treated with different concentrations of CP‐31398 (1, 2, 4, 6, 8, and 10 μg/ml) to determine the optimum concentration using fluorometric microculture cytotoxicity assay. After constructing the sh‐PAX2 vector, CC cells were transfected with sh‐PAX2 or treated with CP‐31398. The effects of CP‐31398 or PAX2 silencing on CC cell proliferation, apoptosis, invasion, and migration were evaluated. Epithelial mesenchymal transition (EMT)‐related genes such as E‐cadherin, vimentin, N‐cadherin, snail, and twist in CC cells were detected. Tumor formation experiment in nude mice was performed to observe tumor growth. The optimum concentration of CP‐31398 was 2 μg/ml. PAX2 was overexpressed in CC cells. CC cells treated with CP‐31398 or treated with sh‐PAX2 inhibited proliferation, invasion, and migration but promoted apoptosis with decreased PAX2 expression. The EMT process in CC cells was also reversed after treatment with CP‐31398 or sh‐PAX2. Moreover, the tumor formation experiment in nude mice revealed the inhibitory activity of CP‐31398 in CC tumor in nude mice by suppressing PAX2. Our results provide evidence that CP‐31398 could inhibit EMT and promote apoptosis of CC cells to curb CC tumor growth by downregulating PAX2. Our results provide evidence that CP‐31398 could inhibit EMT and promote apoptosis of CC cells to curb CC tumor growth by downregulating PAX2.