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Int J Oncol. 2019 Jan 9. doi: 10.3892/ijo.2019.4681. [Epub ahead of print]

CP‑31398 attenuates endometrial cancer cell invasion, metastasis and resistance to apoptosis by downregulating MDM2 expression.

Author information

1
Department of Gynecologic Oncology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
2
Laboratory of Tumor Precision Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
3
Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
4
Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Abstract

Endometrial cancer (EC) is one of the most common malignancies of the female reproductive system, and metastasis is a major cause of mortality. In this study, we aimed to explore the role of CP‑31398 in the migration, invasion and apoptosis of EC cells by its regulation of the expression of the murine double minute 2 (MDM2) gene. For this purpose, EC tissues and adjacent normal tissues were collected, and the positive expression rate of MDM2 in these tissues was assessed. Subsequently, the cellular 50% inhibitory concentration (IC50) of CP‑31398 was measured. The EC RL95‑2 and KLE cell lines had a higher MDM2 expression and were thus selected for use in subsequent experiments. The EC cells were then treated with CP‑31398 (2 µg/ml), and were transfected with siRNA against MDM2 or an MDM2 overexpression plasmid in order to examine the effects of CP‑31398 and MDM2 on EC cell activities. The expression of p53, p21, Bad, Bax, B‑cell lymphoma‑2 (Bcl‑2), cytochrome c (Cyt‑c), caspase‑3, Cox‑2, matrix metalloproteinase (MMP)‑2 and MMP‑9 was measured to further confirm the effects of CP‑31398 on cell migration, invasion and apoptosis. Our results indicated that MDM2 was highly expressed in EC tissues. Notably, EC cell viability decreased with the increasing concentrations of CP‑31398. The EC cells treated with CP‑31398 or siRNA against MDM2 exhibited an increased apoptosis and a suppressed migration and invasion, corresponding to an increased expression of p53, p21, Bad, Bax, Cyt‑c and caspase‑3, as well as to a decreased expression of Bcl‑2, Cox‑2, MMP‑2 and MMP‑9. Moreover, treatment with CP‑31398 and siRNA against MDM2 further enhanced these effects. Taken together, the findings of this study indicate that the CP‑31398‑mediated downregulation of MDM2 may suppress EC progression via its inhibitory role in EC cell migration, invasion and resistance to apoptosis. Therefore, treatment with CP‑31398 may prove to be possible therapeutic strategy for EC.

PMID:
30628640
DOI:
10.3892/ijo.2019.4681

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