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

02 October 2019 : Clinical Research  

Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling

Yukun Wu1BC, Zhizhang Li1DE, Lijuan Zhang2AEF, Guiyang Liu3AF*

DOI: 10.12659/MSM.919319

Med Sci Monit 2019; 25:7383-7390

Abstract

BACKGROUND: Glioblastoma, the most common and malignant glial tumor, often has poor prognosis. Tivantinib has shown its potential in treating c-Met-high carcinoma. No studies have explored whether tivantinib inhibits the development of glioblastoma.

MATERIAL AND METHODS: The correlation between c-Met expression and clinicopathological characteristics of glioblastoma was investigated. U251 and T98MG glioblastoma cells treated with tivantinib, PI3K inhibitor (LY294002), PI3K activator (740 Y-P), and/or mammalian target of rapamycin (mTOR) inhibitor were subjected to MTT assay or colony formation assay to evaluate cell proliferation. The expression of mTOR signaling and caspase-3 in tivantinib-treated glioblastoma cells was differentially measured by western blotting.

RESULTS: In a group of Chinese patients, expression of c-Met was elevated with the size of glioblastoma, but not with the other clinicopathological characteristics, including gender, age, grade, IDH status, 1p/19q status, and Ki67 status. High dose of tivantinib (1 μmol/L) obviously repressed the proliferation and colony formation of U251 and T98MG glioblastoma cells, but low dose (0.1 μmol/L) of tivantinib failed to retard cell proliferation. Tivantinib blocked PI3K/Akt/mTOR signaling but did not change the expression of cleaved caspase-3. PI3K activator 740 Y-P (20 μmol/L) significantly rescued tivantinib-induced decrease of cell proliferation. Tivantinib (1 μmol/L) in combination with PI3K inhibitor LY294002 (0.5 μmol/L) and mTOR inhibitor rapamycin (0.1 nmol/L) largely inhibited the proliferation of glioblastoma cells.

CONCLUSIONS: c-MET inhibitor tivantinib blocks PIKE/Akt/mTOR signaling and hampers the proliferation of glioblastoma cells, which endows the drug a therapeutic effect.

Keywords: Glioblastoma, TOR Serine-Threonine Kinases

0 Comments

Editorial

01 August 2022 : Editorial  

Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937927

Med Sci Monit 2022; 28:e937927

In Press

08 Aug 2022 : Clinical Research  

A 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Comp...

Med Sci Monit In Press; DOI: 10.12659/MSM.937331  

08 Aug 2022 : Clinical Research  

Hemoglobin/Red Blood Cell Distribution Width Ratio in Peripheral Blood Is Positively Associated with Progno...

Med Sci Monit In Press; DOI: 10.12659/MSM.937146  

05 Aug 2022 : Clinical Research  

A Retrospective Study of 98 Elderly Patients with High-Risk Lateral Femoral Wall Intertrochanteric Hip Frac...

Med Sci Monit In Press; DOI: 10.12659/MSM.936923  

04 Aug 2022 : Clinical Research  

Radiological Assessment of Prevalance and Quality of Periapical Status of Endodontic Treatments

Med Sci Monit In Press; DOI: 10.12659/MSM.936569  

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