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

Abstract

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.

• Authors: Ling Liu, Tan-Tan Yu, Chen-Chen Ren, Li Yang, Shi-Hong Cui, Xiao-An Zhang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 3 Pg. 2929-2942 (03 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30132866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• PAX2 Transcription Factor
• PAX2 protein, human
• Pyrimidines
• CP 31398

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Progression
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Heterografts
• Humans
• Mice
• PAX2 Transcription Factor (genetics)
• Pyrimidines (pharmacology)
• Uterine Cervical Neoplasms (drug therapy, genetics, pathology)