Introduction of WT-TP53 into pancreatic cancer cells alters sensitivity to chemotherapeutic drugs, targeted therapeutics and nutraceuticals

Publication date: Available online 28 June 2018Source: Advances in Biological RegulationAuthor(s): Stephen L. Abrams, Kvin Lertpiriyapong, Li V. Yang, Alberto M. Martelli, Lucio Cocco, Stefano Ratti, Marco Falasca, Ramiro M. Murata, Pedro L. Rosalen, Paolo Lombardi, Massimo Libra, Saverio Candido, Giuseppe Montalto, Melchiorre Cervello, Linda S. Steelman, James A. McCubreyAbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5–10%. Mutations at the TP53 gene are readily detected in pancreatic tumors isolated from PDAC patients. We have investigated the effects of restoration of wild-type (WT) TP53 activity on the sensitivity of pancreatic cancer cells to: chemotherapy, targeted therapy, as well as, nutraceuticals. Upon introduction of the WT-TP53 gene into the MIA-PaCa-2 pancreatic cancer cell line, the sensitivity to drugs used to treat pancreatic cancer cells such as: gemcitabine, fluorouracil (5FU), cisplatin, irinotecan, oxaliplatin, and paclitaxel increased significantly. Likewise, the sensitivity to drugs used to treat other cancers such as: doxorubicin, mitoxantrone, and 4 hydroxy tamoxifen (4HT) also increased upon introduction of WT-TP53 into MIA-PaCa-2 cells. Furthermore, the sensitivity to certain inhibitors which target: PI3K/mTORC1, PDK1, SRC, GSK-3, and biochemical processes such as proteasomal degradation a...
Source: Advances in Biological Regulation - Category: Biology Source Type: research