Unknown

Dataset Information

0

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


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 ?2? 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.

SUBMITTER: Kong X 

PROVIDER: S-EPMC6908942 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Kong Xiangnan X   Li Min M   Shao Kai K   Yang Yinrong Y   Wang Qian Q   Cai Meijuan M  

Oncology reports 20191031 1


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 presen  ...[more]

Similar Datasets

| S-EPMC8504816 | biostudies-literature
| S-EPMC7185589 | biostudies-literature
| S-EPMC6305136 | biostudies-literature
| S-EPMC6754436 | biostudies-literature
| S-EPMC6587853 | biostudies-literature
| S-EPMC3043635 | biostudies-literature
| S-EPMC6940394 | biostudies-literature
| S-EPMC5003392 | biostudies-literature
| S-EPMC2579379 | biostudies-literature
| S-EPMC8065989 | biostudies-literature