Smad4 induces cell death in HO-8910 and SKOV3 ovarian carcinoma cell lines via PI3K-mTOR involvement
| Autor: | Yushuang Yao, Zhuqing Mao, Chuan Li, Fanmao Kong, Zhe Zhang, Aiping Chen, Zhaoyuan Niu |
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| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
animal structures Apoptosis Carcinoma Ovarian Epithelial General Biochemistry Genetics and Molecular Biology Phosphatidylinositol 3-Kinases Ovarian carcinoma Cell Line Tumor Autophagy Medicine Humans PI3K/AKT/mTOR pathway Original Research Smad4 Protein integumentary system business.industry TOR Serine-Threonine Kinases digestive system diseases Cell culture embryonic structures Cancer research Female biological phenomena cell phenomena and immunity business Corrigendum |
| Zdroj: | Exp Biol Med (Maywood) |
| ISSN: | 1535-3699 |
| Popis: | Ovarian carcinoma is one of the most common malignant cancers in women. Previous research has shown that Smad4 participates in the progression of multiple biological reactions as a crucial regulator. Nevertheless, studies on the role of Smad4 in ovarian carcinoma have been extremely limited. The study aim was to explore the mechanism underlying Smad4 regulation of HO-8910 and SKOV3 cell viability and autophagy. We observed that Smad4 gene expression in ovarian carcinoma tissues and cell lines was downregulated, and Smad4 overexpression resulted in decreased proliferation and increased autophagy in HO-8910 and SKOV3 cells (ovarian carcinoma cells). We also found that Smad4 overexpression induced apoptosis of ovarian carcinoma cells. A co-immunoprecipitation assay also revealed that Smad4 interacted with the P85 subunit of PI3K and caused its degradation and dephosphorylation. Subsequently, expression of mTOR was inhibited. Accordingly, these findings showed that further investigation of the biological mechanisms underlying ovarian carcinoma occurrence and progression is warranted, which may lead to new ovarian carcinoma treatment strategies. Impact statement This study investigated the effect and mechanism of Smad4 in ovarian carcinoma (OC) cell viability and demonstrated that Smad4 acted as a tumor suppressor in OC, which may contribute to the understanding of molecular mechanisms underlying OC occurrence and progression. Smad4 expression was decreased in the OC specimens, but Smad4 recovery in the OC cell lines impaired the survival and viability of OC cells by increasing autophagy and apoptosis. Further investigation showed that Smad4 interacted with the P85 subunit of PI3K and caused deactivation of the PI3K/mTOR pathway. Therefore, Smad4 could be considered as a target in cancer therapy due to its regulatory effect in OC carcinogenesis. |
| Databáze: | OpenAIRE |
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