Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo

BACKGROUND: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate the synergistic effect of clarithromycin (CAM) with cisplatin to inhibit ovarian carcinoma cells growth in vitro and in vivo.

RESULTS: We performed CCK-8 assay to detect apoptosis rates in response to CAM alone or in combination with cisplatin, which were further confirmed by Annexin V and PI staining methods and western blotting. Mechanistically, CAM could reduce endogenous antioxidant enzyme expression and increase the levels of reactive oxygen species (ROS) to augment the cytotoxic effect of cisplatin. Meanwhile, a tumor xenograft model in athymic BALB/c-nude mice demonstrated that CAM combined with cisplatin resulted in reduced tumor growth and weight compared with cisplatin alone.

CONCLUSION: Collectively, our results indicate that CAM works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Journal of ovarian research - 12(2019), 1 vom: 08. Nov., Seite 107

Sprache:

Englisch

Beteiligte Personen:

Zhou, Bo [VerfasserIn]
Xia, Meng [VerfasserIn]
Wang, Bin [VerfasserIn]
Thapa, Niresh [VerfasserIn]
Gan, Lijuan [VerfasserIn]
Sun, Chaoyang [VerfasserIn]
Guo, Ensong [VerfasserIn]
Huang, Jia [VerfasserIn]
Lu, Yulan [VerfasserIn]
Cai, Hongbin [VerfasserIn]

Links:

Volltext

Themen:

Cisplatin
Cisplatin-resistance
Clarithromycin
Combination therapy
H1250JIK0A
Journal Article
Ovarian cancer
Q20Q21Q62J
Reactive Oxygen Species

Anmerkungen:

Date Completed 30.03.2020

Date Revised 30.03.2020

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s13048-019-0570-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM303075597