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Can J Physiol Pharmacol. 2016 May;94(5):526-33. doi: 10.1139/cjpp-2015-0481. Epub 2016 Feb 25.

Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.

Zhao Y1, Wang X1, Li L1,1, Li C1,1.

Author information

1
Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Rd., Huaiyin Dist., Jinan 250021, Shandong Province, China.

Abstract

The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

KEYWORDS:

cancer du col de l’utérus; cervical cancer; doxycycline; drug repositioning; energy metabolism; métabolisme énergétique; réaffectation de médicaments

PMID:
26913972
DOI:
10.1139/cjpp-2015-0481
[Indexed for MEDLINE]

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