Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination
Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Multidrug resistance remains a major obstacle to successful treatment for patients. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect. In t...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223008648 |
| _version_ | 1797744140206735360 |
|---|---|
| author | Xiaochen Qiu Juan Wang Nan Zhang Tongde Du Lin Chen Hongqing Xi |
| author_facet | Xiaochen Qiu Juan Wang Nan Zhang Tongde Du Lin Chen Hongqing Xi |
| author_sort | Xiaochen Qiu |
| collection | DOAJ |
| description | Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Multidrug resistance remains a major obstacle to successful treatment for patients. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect. In this study, we have investigated the effect of estradiol cypionate (ECP) on gastric cancer in vitro and vivo. Our data show that ECP inhibited the proliferation, promoted apoptosis, and caused G1/S phase arrest of gastric cancer cells. The mechanism by which ECP promoted apoptosis of gastric cancer cells was related to the downregulation of AKT protein expression caused by the increased ubiquitination modification levels of AKT, which finally inhibited the over-activation of the PI3K-AKT-mTOR signaling pathway. In vivo tumorigenesis experiments showed that ECP significantly inhibited the growth of gastric cancer cells, showing promise for clinical application. The above findings indicate that ECP inhibited the growth of gastric cancer and induced apoptosis through the PI3K /Akt/mTOR pathway. In summary, the efficacy showed in our data suggests that ECP is a promising anti-tumor compound for gastric cancer. |
| first_indexed | 2024-03-12T15:05:28Z |
| format | Article |
| id | doaj.art-895f89b8b51e4b51a9ef0cde4845951e |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T15:05:28Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-895f89b8b51e4b51a9ef0cde4845951e2023-08-13T04:52:29ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115073Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitinationXiaochen Qiu0Juan Wang1Nan Zhang2Tongde Du3Lin Chen4Hongqing Xi5Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; Medical School of Chinese PLA, Beijing, ChinaDepartment of Oncology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, Jiangsu, 215123, ChinaMedical School of Chinese PLA, Beijing, China; Department of Gastrointestinal Surgery, Shanghai Fourth People's Hospital, School of Medicine, Tongi Uni-versuty, Shanghai 200434, ChinaSuzhou Institute of Systems Medicine, No. 100 Chongwen Road, Suzhou City, Suzhou 215000, China; Co-corresponding author.Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; Medical School of Chinese PLA, Beijing, China; Co-corresponding author.Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; Medical School of Chinese PLA, Beijing, China; Corresponding author at: Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Multidrug resistance remains a major obstacle to successful treatment for patients. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect. In this study, we have investigated the effect of estradiol cypionate (ECP) on gastric cancer in vitro and vivo. Our data show that ECP inhibited the proliferation, promoted apoptosis, and caused G1/S phase arrest of gastric cancer cells. The mechanism by which ECP promoted apoptosis of gastric cancer cells was related to the downregulation of AKT protein expression caused by the increased ubiquitination modification levels of AKT, which finally inhibited the over-activation of the PI3K-AKT-mTOR signaling pathway. In vivo tumorigenesis experiments showed that ECP significantly inhibited the growth of gastric cancer cells, showing promise for clinical application. The above findings indicate that ECP inhibited the growth of gastric cancer and induced apoptosis through the PI3K /Akt/mTOR pathway. In summary, the efficacy showed in our data suggests that ECP is a promising anti-tumor compound for gastric cancer.http://www.sciencedirect.com/science/article/pii/S0753332223008648Estradiol cypionateGastric cancerProliferationApoptosisAKT |
| spellingShingle | Xiaochen Qiu Juan Wang Nan Zhang Tongde Du Lin Chen Hongqing Xi Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination Biomedicine & Pharmacotherapy Estradiol cypionate Gastric cancer Proliferation Apoptosis AKT |
| title | Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination |
| title_full | Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination |
| title_fullStr | Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination |
| title_full_unstemmed | Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination |
| title_short | Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination |
| title_sort | estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating akt ubiquitination |
| topic | Estradiol cypionate Gastric cancer Proliferation Apoptosis AKT |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223008648 |
| work_keys_str_mv | AT xiaochenqiu estradiolcypionateinhibitsproliferationandpromotesapoptosisofgastriccancerbyregulatingaktubiquitination AT juanwang estradiolcypionateinhibitsproliferationandpromotesapoptosisofgastriccancerbyregulatingaktubiquitination AT nanzhang estradiolcypionateinhibitsproliferationandpromotesapoptosisofgastriccancerbyregulatingaktubiquitination AT tongdedu estradiolcypionateinhibitsproliferationandpromotesapoptosisofgastriccancerbyregulatingaktubiquitination AT linchen estradiolcypionateinhibitsproliferationandpromotesapoptosisofgastriccancerbyregulatingaktubiquitination AT hongqingxi estradiolcypionateinhibitsproliferationandpromotesapoptosisofgastriccancerbyregulatingaktubiquitination |