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
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
08 Mar 2024 : Laboratory Research
Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Res...Med Sci Monit In Press; DOI: 10.12659/MSM.944110
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
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
01 Jan 2022 : Editorial
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