Synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells

This study explored the synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells by treating HNE-1 and cisplatin (diamminedichloroplatinum; DDP)-resistant HNE1/DDP nasopharyngeal cancer cell lines with DDP, autophagy inhibitors, or a combination of autophagy inhibitors and DDP. Cell viability was determined via MTT (colorimetric) and colony-forming assays, and the rate of apoptosis was determined using propidium iodide (PI) and annexin V double-staining. The expressions of proteins were determined by Western blotting. For our in-vivo studies, a murine xenograft model was established to evaluate the anti-tumor effects of the combination of autophagy inhibitor and DDP. The results showed that treatment with DDP increased the expressions of ATP-binding cassette sub-family B member 1 (ABCB1), ATP Binding Cassette Subfamily C Member 1 (ABCC1), and P-glycoprotein 1 (P-gp) in the HNE1/DDP cell lines. Treatment with chloroquine decreased the expression levels of ABCB1, ABCC1, and P-gp, and increased the formation of LC3-II and the expression levels of p62 in the HNE1/DDP cells. Additionally, the combination of autophagy inhibitors and DDP produced a synergistic effect on DDP-induced cell death and apoptosis. Furthermore, the combination of the autophagy inhibitor and DDP showed significant anti-tumor effects in the xenograft mouse model. In summary, autophagy inhibitors show synergistic anti-tumor effects with DDP in vitro against DDP-resistant nasopharyngeal cancer cells and in vivo in our xenograft murine model.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:99

Enthalten in:

Biochemistry and cell biology = Biochimie et biologie cellulaire - 99(2021), 3 vom: 01. Juni, Seite 322-329

Sprache:

Englisch

Beteiligte Personen:

Yin, Wei [VerfasserIn]
Xu, Jianfeng [VerfasserIn]
Mao, Yanjiao [VerfasserIn]

Links:

Volltext

Themen:

Aldehydes
Autophagie
Autophagy
Cancer du nasopharynx
Chloroquine
Cisplatin
Cisplatine
HNE1/DDP
Journal Article
Nasopharyngeal cancer
Q20Q21Q62J
Research Support, Non-U.S. Gov't
Tert-4-hydroxy-2-nonenal

Anmerkungen:

Date Completed 28.09.2021

Date Revised 28.09.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1139/bcb-2020-0283

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM325871191