@article{b401c35d2ded44b0a936184bbb95818d,
title = "Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells",
abstract = "Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA-mutant colorectal carcinoma, but not in PIK3CA-wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA-mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA-mutant colon cancer cells than for PIK3CA-wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA-mutant and six PIK3CA-wildtype human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A > G (p.H1047R) or c.1633G > A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA-mutant cells than in PIK3CA-wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA-mutant cells than in PIK3CA-wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A > G (p.H1047R) or c.1633G > A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA-mutated colon cancer cells than in PIK3CAwild- type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA-mutant colon cancer.",
keywords = "Anti-tumor effect, Colorectal cancer, Isogenic cell model, NSAID, PI3K",
author = "Mancang Gu and Reiko Nishihara and Yang Chen and Wanwan Li and Yan Shi and Yohei Masugi and Tsuyoshi Hamada and Keisuke Kosumi and Li Liu and {da Silva}, Annacarolina and Nowak, {Jonathan A.} and Tyler Twombly and Chunxia Du and Hideo Koh and Wenbin Li and Meyerhardt, {Jeffrey A.} and Wolpin, {Brian M.} and Marios Giannakis and Aguirre, {Andrew J.} and Bass, {Adam J.} and Drew, {David A.} and Chan, {Andrew T.} and Fuchs, {Charles S.} and Qian, {Zhi Rong} and Shuji Ogino",
note = "Funding Information: Healthcare, Pfizer Inc., and Aralez Pharmaceuticals. This study was not funded by Bayer Healthcare, Pfizer Inc. or Aralez Pharmaceuticals. No other conflict of interest exists. The other authors declare that they have no conflicts of interest. Funding Information: This work was supported by U.S. National Institutes of Health (NIH) grants (P50 CA127003 to C.S.F.; R01 CA137178 to A.T.C.; K24 DK098311 to A.T.C.; R35 CA197735 to S.O.; and K07 CA190673 to R.N.); Nodal Award (to S.O.) from the Dana-Farber Harvard Cancer Center; and the Project P Fund. M.Gu. was supported by a scholarship grant from Chinese Scholarship Council, National Natural Science Foundation of China grants (81673607, 81303235) and a fellowship from Zhejiang Chinese Medical University. K.K. was supported by a grant from Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japanese Society for the Promotion of Science. Z.R.Q. was supported by Medical Oncology Translational Grant Program from Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School. Publisher Copyright: {\textcopyright} Gu et al.",
year = "2017",
doi = "10.18632/oncotarget.20972",
language = "English",
volume = "8",
pages = "87379--87389",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "50",
}