Novel Therapeutic Strategy To Inhibit Growth Of Pancreatic Cancer Organoids Using A Rational Combination Of Drugs To Induce Mitotic Arrest And Apoptosis.
JOURNAL OF CLINICAL ONCOLOGY(2018)
Abstract
322Background: The ability of cancer cells to suppress apoptosis is critical for carcinogenesis. The Bcl-2-family of regulator proteins, including the anti-apoptotic members Bcl-2, Bcl-xL and Mcl-1, contributes to a complex network in control of apoptosis. BH3-mimetics (e.g. ABT-263) can inhibit anti-apoptotic Bcl-2 proteins and therefore have been developed as potential cancer therapeutics. Aurora Kinase A (AKA) is over-expressed in pancreatic cancer (PC) and is expressed to regulate G2-M transition during mitosis, making it an attractive target for PC. In this study we hypothesized that a combination of mitotic arrest using an AKA inhibitor (e.g. MLN8237) would sensitize PC to induction of apoptosis by a BH3-mimetic. Methods: Pancreatic cell lines (AsPC-1, PANC-1, MIA PaCa-2, HPAF-II) and patient-derived pancreatic cancer organoids (PDO) were treated with a BH3-mimetic (ABT-263) alone, an AKA inhibitor (MLN8237) alone, or the combination in comparison to untreated controls. Cell viability was measured u...
MoreTranslated text
Key words
pancreatic cancer organoids,novel therapeutic strategy,apoptosis,mitotic arrest
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined