Role of FOXO protein's abnormal activation through PI3K / AKT pathway in platinum resistance of ovarian cancer
| Autor: | Xiang-Tian Meng, Ya-Nan Xu, Yun-Yue Shi, Xiu-Juan Tian |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
endocrine system
endocrine system diseases DNA damage medicine.medical_treatment Apoptosis Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine medicine Humans Transcription factor PI3K/AKT/mTOR pathway Ovarian Neoplasms Chemotherapy 030219 obstetrics & reproductive medicine business.industry Obstetrics and Gynecology Cancer Forkhead Transcription Factors medicine.disease female genital diseases and pregnancy complications Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Cancer cell Cancer research Female Ovarian cancer business Proto-Oncogene Proteins c-akt |
| Zdroj: | Journal of Obstetrics and Gynaecology Research. 47:1946-1957 |
| ISSN: | 1447-0756 1341-8076 |
| DOI: | 10.1111/jog.14753 |
| Popis: | Aim Platinum-based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum-resistant ovarian cancer. Methods We reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum-resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature. Results Ovarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM-Chk2-p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum-resistant ovarian cancer cell model, it was found that FoxO-1 is decreased in platinum-resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum-induced apoptosis may further guide the treatment of platinum-resistant ovarian cancer. Conclusions There are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re-understand the role that FOXOs have played in cancer development and treatment. |
| Databáze: | OpenAIRE |
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