Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

08 June 2019 : Laboratory Research  

Knockdown of Hypoxia-Inducible Factor 1α (HIF-1α) Promotes Autophagy and Inhibits Phosphatidylinositol 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Ovarian Cancer Cells

Jinling Huang1ABCDEFG, Likun Gao1A, Bingshu Li1BC, Cheng Liu1D, Shasha Hong1E, Jie Min1F, Li Hong1G*

DOI: 10.12659/MSM.915730

Med Sci Monit 2019; 25:4250-4263


BACKGROUND: Ovarian cancer has the highest mortality rate among all female genital tumors because of its insidious onset and drug resistance. Hypoxia-inducible factor 1α (HIF-1α), one of the best-studied oncogenes, plays an important part in tumor adaptation to microenvironmental hypoxia and was found to be overexpressed in several malignancies, including ovarian cancer. Previous studies found that the effect of HIF-1α on cancers may be correlated with autophagy and some signaling pathways, such as PI3K/AKT/mTOR, in several tumors. However, the function and potential mechanism have not been clearly defined.

MATERIAL AND METHODS: The expression of HIF-1α in ovarian cancer tissues were detected by immunohistochemistry. HIF-1α was knocked down by siRNA transfection. Cell viability was examined by CCK8 and colony formation assay. Apoptosis and autophagy were detected with flow cytometry, transmission electron microscopy, and laser scanning confocal microscopy, respectively. The proteins related to autophagy and PI3K/AKT/mTOR were detected through Western blot analysis.

RESULTS: HIF-1α was expressed at higher levels in epithelial or metastatic ovarian cancer tissue than in normal fallopian tube tissue. When HIF-1α was knocked down by siRNA in A2780 and SKOV3 cells, the viability of ovarian cancer cells was weakened, but the apoptosis and autophagy were strengthened. Accordingly, autophagosome formation increased and the expression of autophagy-related proteins LC3 and P62 increased in HIF-1α knockdown cells. The PI3K/Akt/mTOR signaling pathway was also found to be inactivated in HIF-1α knockdown cells.

CONCLUSIONS: These findings show that knockdown of HIF-1α promoted autophagy and inhibited the PI3K/AKT/mTOR signaling pathway in ovarian cancer cells.

Keywords: Autophagy, Hypoxia-Inducible Factor 1, alpha Subunit, Ovarian Neoplasms, Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases, Apoptosis, Carcinoma, Ovarian Epithelial, Cell Hypoxia, Cell Survival, Drug Resistance, Neoplasm, Gene Knockdown Techniques, phosphatidylinositol 3-kinase, Proto-Oncogene Proteins c-akt, RNA, Small Interfering



12 September 2022 : Editorial  

Editorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)

Ana Luisa Ordóñez-Vázquez, Sofía Murúa Beltrán-Gall, Shreya C. Pal, Nahum Méndez-Sánchez
Liver Research Unit, Medica Sur Clinic Foundation, Mexico City, Mexico

DOI: 10.12659/MSM.938365

Med Sci Monit 2022; 28:e938365


16 September 2022 : Review article  

Effects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Rev...

Med Sci Monit In Press; DOI: 10.12659/MSM.938141  

12 September 2022 : Clinical Research  

Effect of Vitamin D Concentration on Course of COVID-19

Med Sci Monit In Press; DOI: 10.12659/MSM.937741  

In Press

23 Sep 2022 : Review article  

A Review of the Role of Ultrasound Radiomics and Its Application and Limitations in the Investigation of Th...

Med Sci Monit In Press; DOI: 10.12659/MSM.937738  

23 Sep 2022 : Review article  

Review of the Long-Term Outcomes of Guided Bone Regeneration and Autologous Bone Block Augmentation for Ver...

Med Sci Monit In Press; DOI: 10.12659/MSM.937433  

22 Sep 2022 : Clinical Research  

Comparison of Incremental Shuttle Walking Test, 6-Minute Walking Test, and Cardiopulmonary Exercise Stress ...

Med Sci Monit In Press; DOI: 10.12659/MSM.938140  

21 Sep 2022 : Clinical Research  

Questionnaire-Based Study on the Prevalence, Awareness, and Preventive Measures of Occupational Hazards Amo...

Med Sci Monit In Press; DOI: 10.12659/MSM.938084  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750