PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib.

ABSTRACT:

Objectives

Cervical cancer (CC) remains a major health problem worldwide. Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutics in ovarian cancer. We explored the preclinical in vitro and in vivo activity of olaparib against multiple primary whole exome sequenced (WES) CC cells lines and xenografts.

Methods

Olaparib cell-cycle, apoptosis, homologous-recombination-deficiency (HRD), PARP trapping and cytotoxicity activity was evaluated against 9 primary CC cell lines in vitro. PARP and PAR expression were analyzed by Western blot assays. Finally, olaparib in vivo antitumor activity was tested against CC xenografts.

Results

While none of the cell lines demonstrated HRD, three out of 9 (33.3%)

SUBMITTER: Bianchi A 

PROVIDER: S-EPMC6788971 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature