@misc{10481/77618,
year = {2022},
month = {9},
url = {https://hdl.handle.net/10481/77618},
abstract = {Pancreatic cancer (PC) is one of the tumors with the lowest survival rates due to the poor efficacy of the
treatments currently used. Gemcitabine (GMZ), one of the chemotherapeutic agents employed when the tumor is
unresectable, frequently fails due to the development of drug resistance. PARP1 is a relevant protein in this
phenomenon and appears to be related to cancer progression in several types of tumors, including PC. To
determine the relevance of PARP1 in the development and treatment of PC, we used the Panc02 cell line to
generate modified PC cells with stably inhibited PARP1 expression (Panc02-L) and used GMZ, Olaparib (OLA)
and GMZ+OLA as therapeutic strategies. Viability, radiosensitization, angiogenesis, migration, colony formation,
TUNEL, cell cycle, multicellular tumorsphere induction and in vivo assays were performed to test the influence of
PARP1 inhibition on resistance phenomena and tumor progression. We demonstrated that stable inhibition or
pharmacological blockade of PARP1 using OLA-sensitized Panc02 cells against GMZ significantly decreased their
IC50, reducing colony formation capacity, cell migration and vessel formation (angiogenesis) in vitro. Furthermore,
in vivo analyses revealed that Panc02-L-derived (PARP1-inhibited) tumors showed less growth and
lethality, and that GMZ+OLA treatment significantly reduced tumor growth. In conclusion, PARP1 inhibition,
both alone and in combination with GMZ, enhances the effectiveness of this chemotherapeutic agent and represents
a promising strategy for the treatment of PC.},
organization = {Granada University and ibs. GRANADA	INB-009},
organization = {Instituto de Salud Carlos III
European Commission	DTS17/00081},
organization = {Junta de Andalucia (FEDER) (Spain)	CTS-107
A-CTS-666UGR20
B-CTS-122-UGR20},
organization = {Ministerio de Educaci 'on, Ciencia y Deporte y Competitividad (Spain)},
publisher = {Elsevier},
keywords = {PARP1},
keywords = {Pancreatic cancer},
keywords = {Olaparib},
keywords = {Gemcitabine},
keywords = {Drug resistance},
title = {PARP1 inhibition by Olaparib reduces the lethality of pancreatic cancer cells and increases their sensitivity to Gemcitabine},
doi = {10.1016/j.fm.2022.104068},
author = {Quiñonero Muñoz, Francisco José and Mesas Hernández, Cristina and Muñoz Gámez, José Antonio and Jiménez Luna, Cristina and Perazzoli, Gloria and Prados Salazar, José Carlos and Melguizo Alonso, Consolación and Ortiz Quesada, Raúl},
}