272P - Melatonin increases the chemosensitivity of diffuse large Bell lymphoma cells to Epirubicin by inhibiting P-glycoprotein expression via the NF-κB pathway

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.