Abstract 272P
Background
Epirubicin (EPI) is a first-line chemotherapeutic drug for the clinical treatment of diffuse large B cell lymphoma (DLBCL), but the overexpression of multidrug resistance (MDR) transporter proteins, such as P-glycoprotein (P-gp), renders EPI ineffective. On the basis of some studies, melatonin (MLT) is considered to possess the potential for chemotherapeutic synergy that can be leveraged to overcome MDR.
Methods
The human DLBCL cells SUDHL-6 and SUDHL-10 were incubated with MLT and/or EPI for 48 h. Using CCK8 assay, the cell viability of SUDHL-10 and SUDHL-6 cell lines under different treatments were tested. Using AO/EB assay ,the apoptosis of SUDHL-6 cell line was detected. Cytochrome c release experiment was used to reveal the further molecular mechanism. Immunofluorescence experiment was used to detect the expression of P-gp of DLBCL cell lines under different drug treatment groups. Rhodamine-123 and epirubicin accumulation test were used to detect the function of P-gp. Immunohistochemical staining studies in tumor tissue of DLBCL disclosed that the expression of P-gp and P65. Western blotting assay and pulldown assay were used to detect the relationship between NF-κB pathway and P-gp exression.
Results
Melatonin potentiated the epirubicin-mediated inhibition of cell proliferation and increased epirubicin-induced apoptosis. Melatonin inhibits epirubicin-induced P-glycoprotein expression and the activity of the P-glycoprotein pump.Epirubicin promotes the expression of P-gp by activating the NF-κB pathway. However, melatonin inhibited the epirubicin-mediated activation of NF-κB signaling and the expression of P-gp.
Conclusions
Our results demonstrated that MLT inactivating the NF-κB pathway and down-regulating the expression of P-gp, ultimately sensitized EPI-mediated growth suppression of DLBCL cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The second hospital of Dalian medical university.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
41P - Clinical verification on the relationship between serum lipid metabolism and the immune microenvironment in breast cancer patients
Presenter: Wataru Goto
Session: Poster display session
Resources:
Abstract
42P - Genome wide copy number analysis of circulating tumour cells in breast cancer liver metastasis
Presenter: Saber Imani
Session: Poster display session
Resources:
Abstract
43P - A hotspot variants p.H1047R and p.H1047L in p110α/ΔNp63α complex affects structure, function and contributes to susceptibility metastatic breast cancer
Presenter: Zou Linglin
Session: Poster display session
Resources:
Abstract
44P - Correlation of circulating tumour cells with PET-CT in metastatic breast cancer
Presenter: Venkata Pradeep Babu Koyyala
Session: Poster display session
Resources:
Abstract
45P - The challenge of evaluating new targeted therapies: Opportunities in stratifying the therapeutic response per tumour location
Presenter: Hubert Beaumont
Session: Poster display session
Resources:
Abstract
46P - Plasma soluble CD36 of breast cancer based on pathological and clinical characteristics
Presenter: Aditia Romadhoni
Session: Poster display session
Resources:
Abstract
47P - Investigation of the use of a novel S-1 administration method for treating metastatic and recurrent breast cancer
Presenter: MAYUKO MIKI
Session: Poster display session
Resources:
Abstract
48P - Development of MDA-MB-231-3D-Spheroid as a reliable model for studying Nav1.5 and nNav1.5-mediated breast cancer metastasis
Presenter: Ahmad Murtadha
Session: Poster display session
Resources:
Abstract
49P - Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer
Presenter: Alshimaa Alhanafy
Session: Poster display session
Resources:
Abstract
50P - Prognostic factors of recurrence or distant metastasis in elderly breast cancer patients
Presenter: Seungju Lee
Session: Poster display session
Resources:
Abstract