02 October 2019 : Clinical Research
Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) SignalingYukun Wu1BC, Zhizhang Li1DE, Lijuan Zhang2AEF, Guiyang Liu3AF*
Med Sci Monit 2019; 25:7383-7390
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: TOR Serine-Threonine Kinases
01 February 2023 : EditorialEditorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread
Med Sci Monit 2023; 29:e939580
19 January 2023 : Clinical ResearchEvaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...
Med Sci Monit In Press; DOI: 10.12659/MSM.938892
19 January 2023 : Clinical ResearchDetermining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...
Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical ResearchEffect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...
Med Sci Monit 2022; 28:e938926
01 Feb 2023 : Clinical ResearchComparison of 3 Enzyme-Linked Immunoassay Methods to Evaluate Serum Concentrations of Infliximab and Antibo...
Med Sci Monit In Press; DOI: 10.12659/MSM.939084
31 Jan 2023 : Clinical ResearchBalloon Dilation Eustachian Tuboplasty Combined with Tympanotomy Tube Insertion for Treatment of Refractory...
Med Sci Monit In Press; DOI: 10.12659/MSM.938879
31 Jan 2023 : Clinical ResearchComparison of Vision Correction and Corneal Thickness at 180-Day Follow-Up After Femtosecond Laser-Assisted...
Med Sci Monit In Press; DOI: 10.12659/MSM.939099
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292