Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer Retraction in /10.3892/or.2024.8777

Kong,Xiangnan; Li,Min; Shao,Kai; Yang,Yinrong; Wang,Qian; Cai,Meijuan

doi:10.3892/or.2019.7396

Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

Retraction in: /10.3892/or.2024.8777

Authors:
- Xiangnan Kong
- Min Li
- Kai Shao
- Yinrong Yang
- Qian Wang
- Meijuan Cai
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Affiliations: Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: October 31, 2019 https://doi.org/10.3892/or.2019.7396
Pages: 121-132
Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometrial cancer (EC) is one of the most common malignant gynecological tumors in women. The main treatments for EC (surgery, chemotherapy and radiation therapy) produce significant side effects. Thus, it is urgent to identify promising therapeutic targets and prognostic markers. CACNA2D3, as a member of the calcium channel regulatory α2δ subunit family, is reported to exert a tumor suppressive effect in numerous cancers. However, the function of CACNA2D3 in EC is not well known. In the present study, CACNA2D3 was lowly expressed in EC tissues and cells. The overexpression of CACNA2D3 via lentiviral particle injection significantly blocked the tumor growth in an in vivo xenograft model. In vitro, the overexpression of CACNA2D3 markedly inhibited cell proliferation and migration, and promoted cell apoptosis and calcium influx. These data revealed that CACNA2D3 functions as a tumor suppressor in EC. It was also revealed that the addition of progesterone (P4) blocked tumor growth in Ishikawa‑injected nude mice. P4 induced the expression of CACNA2D3 in vivo and in vitro, and the silencing of CACNA2D3 affected P4‑inhibited cell proliferation and P4‑induced cell apoptosis and calcium influx. In Ishikawa cells, P4 enhanced the expression of phosphorylated (p)‑p38 MAPK and PTEN, but blocked the levels of p‑PI3K and p‑AKT. The knockdown of CACNA2D3 blocked the function of P4. These data revealed that P4 promoted cell apoptosis via the activation of the CACNA2D3/Ca2+/p38 MAPK pathway, and blocked cell proliferation via suppression of the PI3K/AKT pathway. Collectively, these findings indicated the antitumor role of CACNA2D3 in EC, and revealed the mechanism of P4 inhibition of EC progression, which provided a new target for EC therapy and new evidence for P4 in EC therapy.

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