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

17 August 2020 : Animal Research

Omipalisib Inhibits Esophageal Squamous Cell Carcinoma Growth Through Inactivation of Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) and ERK Signaling

Dong-shan Zhu1ABCDEF, Jing-yao Dong1BCF, Yao-yao Xu2BCD, Xin-tong Zhang2BCD, Shi-bo Fu2ACEFG, Wei Liu1ACEFG*

DOI: 10.12659/MSM.927106

Med Sci Monit 2020; 26:e927106


BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a life-threatening digestive tract malignancy with no known curative treatment. This study aimed to investigate the antineoplastic effects of omipalisib and its underlying molecular mechanisms in ESCC using a high throughput screen.

MATERIAL AND METHODS: MTT assay and clone formation were used to determine cell viability and proliferation. Flow cytometry was conducted to detect cell cycle distribution and apoptosis. Global gene expression and mRNA expression levels were determined by RNA sequencing and real-time PCR, respectively. Protein expression was evaluated in the 4 ESCC cell lines by Western blot analysis. Finally, a xenograft nude mouse model was used to evaluate the effect of omipalisib on tumor growth in vivo.

RESULTS: In the pilot screening of a 1404-compound library, we demonstrated that omipalisib markedly inhibited cell proliferation in a panel of ESCC cell lines. Mechanistically, omipalisib induced G₀/G₁ cell cycle arrest and apoptosis. RNA-seq, KEGG, and GSEA analyses revealed that the PI3K/AKT/mTOR pathway is the prominent target of omipalisib in ESCC cells. Treatment with omipalisib decreased expression of p-AKT, p-4EBP1, p-p70S6K, p-S6, and p-ERK, therefore disrupting the activation of PI3K/AKT/mTOR and ERK signaling. In the nude mouse xenograft model, omipalisib significantly suppressed the tumor growth in ESCC tumor-bearing mice without obvious adverse effects.

CONCLUSIONS: Omipalisib inhibited the proliferation and growth of ESCC by disrupting PI3K/AKT/mTOR and ERK signaling. The present study supports the rationale for using omipalisib as a therapeutic approach in ESCC patients. Further clinical studies are needed.

Keywords: Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases


Weekly Editorial

25 October 2021 : Editorial

Editorial: The 2021 European Society of Cardiology (ESC) Guidelines on the Real-World Prevention of Atherosclerotic Cardiovascular Disease (ASCVD)

Dinah V. Parums

DOI: 10.12659/MSM.935172

Med Sci Monit 2021; 27:e935172


22 October 2021 : Clinical Research

A Novel Method for the Production of an Autologous Anti-Inflammatory and Anti-Catabolic Product (Cytorich) ...

Med Sci Monit In Press; DOI: 10.12659/MSM.934365  

11 October 2021 : Clinical Research

Clinical Features and Temporal Lung Radiographic Changes in 25 Patients Recovering from COVID-19 Pneumonia:...

Med Sci Monit In Press; DOI: 10.12659/MSM.933381  

08 September 2021 : Clinical Research

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

Med Sci Monit In Press; DOI: 10.12659/MSM.932788  

In Press

25 Oct 2021 : Database Analysis

Impact of Post-Mastectomy Radiation Therapy for Sentinel Lymph Node Micrometastases in Early-Stage Breast C...

Med Sci Monit In Press; DOI: 10.12659/MSM.933275  

22 Oct 2021 : Clinical Research

Ulnar Groove Plasty Guided by a 3D Printing Technique for Moderate to Severe Cubital Tunnel Syndrome Caused...

Med Sci Monit In Press; DOI: 10.12659/MSM.933775  

22 Oct 2021 : Clinical Research

Total Fluoroscopy Time Reduction During Ultrasound- and Fluoroscopy-Guided Percutaneous Transhepatic Biliar...

Med Sci Monit In Press; DOI: 10.12659/MSM.933889  

22 Oct 2021 : Clinical Research

Correlation Between Severity of Illness and Levels of Free Triiodothyronine, Interleukin-6, and Interleukin...

Med Sci Monit In Press; DOI: 10.12659/MSM.933230  

Most Viewed Current Articles

20 Mar 2020 : Clinical Research

Social Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Diseas...

DOI :10.12659/MSM.923921

Med Sci Monit 2020; 26:e923921

15 Apr 2020 : Clinical Research

Psychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...

DOI :10.12659/MSM.924171

Med Sci Monit 2020; 26:e924171

05 May 2020 : Review article

An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development

DOI :10.12659/MSM.924700

Med Sci Monit 2020; 26:e924700

26 Apr 2020 : Clinical Research

Comparison of Prevalence and Associated Factors of Anxiety and Depression Among People Affected by versus P...

DOI :10.12659/MSM.924609

Med Sci Monit 2020; 26:e924609

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