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
195P - HGCSG1601: A retrospective cohort study of the efficacy and safety of nab-paclitaxel plus gemcitabine (nab-P+GEM) for unresectable locally advanced pancreatic cancer (LAPC)
Presenter: Aya Tanimoto
Session: Poster display session
Resources:
Abstract
196P - The tolerability and efficacy of FOLFIRINOX in gastro-oesophageal carcinoma
Presenter: Nicholas Travers
Session: Poster display session
Resources:
Abstract
197TiP - GLOW: Zolbetuximab + CAPOX compared with placebo + CAPOX as first-line treatment for patients with Claudin18.2+/HER2– Locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma: A randomized phase III study
Presenter: Rui-Hua Xu
Session: Poster display session
Resources:
Abstract
198TiP - SPOTLIGHT: Comparison of zolbetuximab or placebo + mFOLFOX6 as first-line treatment in patients with claudin18.2+/HER2– locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ): A randomized phase III study
Presenter: Kensei Yamaguchi
Session: Poster display session
Resources:
Abstract
199TiP - Phase III (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Thomas Yau
Session: Poster display session
Resources:
Abstract
200P - Apalutamide (APA) plus androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC): Analysis of pain and fatigue in the TITAN study
Presenter: Byung Ha Chung
Session: Poster display session
Resources:
Abstract
201P - Efficacy and safety of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC) in the ARAMIS trial
Presenter: Jacob See-tong Pang
Session: Poster display session
Resources:
Abstract
202P - What is the best first-line therapy for metastatic castration-sensitive prostate cancer in 2019? A network meta-analysis
Presenter: Tsz Him So
Session: Poster display session
Resources:
Abstract
203P - Long term outcomes of 2-weekly docetaxel in metastatic high-volume hormone sensitive prostate cancer
Presenter: Suhas Singla
Session: Poster display session
Resources:
Abstract
204P - The effect of radium-223 therapy in agent orange related veterans with metastatic castrate resistance prostate carcinoma (CRPC)
Presenter: Andrew Liman
Session: Poster display session
Resources:
Abstract