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

20 August 2018 : Laboratory Research  

Lapatinib, a Dual Inhibitor of Epidermal Growth Factor Receptor (EGFR) and HER-2, Enhances Radiosensitivity in Mouse Bladder Tumor Line-2 (MBT-2) Cells In Vitro and In Vivo

Yi Mu1ACEG, Deyu Sun1ABCDEF*

DOI: 10.12659/MSM.909865

Med Sci Monit 2018; 24: LBR5811-5819

Abstract

BACKGROUND: The aim of this study was to evaluate the effect of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and HER-2, on the radiosensitivity of murine bladder tumor line-2 (MBT-2) cells in vitro and in vivo.

MATERIAL AND METHODS: MBT-2 cells were pretreated with lapatinib at doses ranging from 200–1,000 nM for 30 min followed by radiation at doses ranging from 2.5–10 Gy for 30 min. A clonogenic assay (colony formation assay) assessed cell survival. Western blot measured phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated AKT (p-AKT), and phosphorylated HER-2 (p-HER2) and the apoptosis marker, PARP. The C3H/HeN mouse tumor xenograft model underwent subcutaneous injection of MBT-2 cells; mice were divided into four groups, treated with lapatinib (200 mg/kg), radiation (15 Gy), a combination of both, and with vehicle (control).

RESULTS: Lapatinib pretreatment, combined with radiation, decreased MBT-2 cell survival, and suppressed radiation-activated levels of p-EGFR and p-HER-2. MBT-2 cells treated with a 10 Gy dose of radiation and 1000 nM of lapatinib showed combination index (CI) values of <1 indicating synergy. Increased expression of γ-H2AX, indicated increased apoptosis. In mice with tumor xenografts, a daily dose of lapatinib (200 mg/kg/day) for seven days combined with radiation on the fourth day suppressed tumor growth to a greater degree than radiation alone.

CONCLUSIONS: Lapatinib treatment enhanced the radiation sensitivity in an in vitro and in vivo murine bladder cancer model by decreasing radiation-mediated EGFR and HER-2 activation, and by causing DNA damage leading to cell apoptosis.

Keywords: Genes, erbB-1, Genes, erbB-2

Add Comment 0 Comments

Editorial

01 June 2024 : Editorial  

Editorial: Concerns as Highly Pathogenic Avian Influenza (HPAI) Virus of the H5N1 Subtype is Identified in Dairy Cows and Other Mammals

Dinah V. Parums

DOI: 10.12659/MSM.945315

Med Sci Monit 2024; 30:e945315

0:00

In Press

Clinical Research  

Comparative Evaluation of Digital Cephalometric Tracing Applications on Mobile Devices and Manual Tracing

Med Sci Monit In Press; DOI: 10.12659/MSM.944628  

0:00

Clinical Research  

Impact of COVID-19-Induced Academic Stress on Insomnia and Suicidal Ideation among Taiwanese Health Trainee...

Med Sci Monit In Press; DOI: 10.12659/MSM.944932  

Review article  

Impact of Workplace Bullying on Nursing Care Quality: A Comprehensive Review

Med Sci Monit In Press; DOI: 10.12659/MSM.944815  

Clinical Research  

Anterior Plate-Supported Cannulated Screw Surgery for Ankle Arthrodesis: Clinical and Radiologic Results in...

Med Sci Monit In Press; DOI: 10.12659/MSM.944452  

Most Viewed Current Articles

17 Jan 2024 : Review article   1,882,405

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research   1,538,203

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research   690,402

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,329

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

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