Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells

Mancang Gu, Reiko Nishihara, Yang Chen, Wanwan Li, Yan Shi, Yohei Masugi, Tsuyoshi Hamada, Keisuke Kosumi, Li Liu, Annacarolina da Silva, Jonathan A. Nowak, Tyler Twombly, Chunxia Du, Hideo Koh, Wenbin Li, Jeffrey A. Meyerhardt, Brian M. Wolpin, Marios Giannakis, Andrew J. Aguirre, Adam J. BassDavid A. Drew, Andrew T. Chan, Charles S. Fuchs, Zhi Rong Qian, Shuji Ogino

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)87379-87389
Number of pages11
JournalOncotarget
Volume8
Issue number50
DOIs
Publication statusPublished - 2017 Jan 1
Externally publishedYes

Fingerprint

Colonic Neoplasms
Aspirin
Neoplasms
Cell Survival
Cell Cycle Resting Phase
Mutation
G1 Phase
Cell Cycle Checkpoints
Colorectal Neoplasms
Cell Cycle
Anti-Inflammatory Agents
Therapeutics
Clone Cells
Apoptosis
Carcinoma
Cell Line

Keywords

  • Anti-tumor effect
  • Colorectal cancer
  • Isogenic cell model
  • NSAID
  • PI3K

ASJC Scopus subject areas

  • Oncology

Cite this

Gu, M., Nishihara, R., Chen, Y., Li, W., Shi, Y., Masugi, Y., ... Ogino, S. (2017). Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells. Oncotarget, 8(50), 87379-87389. https://doi.org/10.18632/oncotarget.20972

Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells. / Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A.; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A.; Wolpin, Brian M.; Giannakis, Marios; Aguirre, Andrew J.; Bass, Adam J.; Drew, David A.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji.

In: Oncotarget, Vol. 8, No. 50, 01.01.2017, p. 87379-87389.

Research output: Contribution to journalArticle

Gu, M, Nishihara, R, Chen, Y, Li, W, Shi, Y, Masugi, Y, Hamada, T, Kosumi, K, Liu, L, da Silva, A, Nowak, JA, Twombly, T, Du, C, Koh, H, Li, W, Meyerhardt, JA, Wolpin, BM, Giannakis, M, Aguirre, AJ, Bass, AJ, Drew, DA, Chan, AT, Fuchs, CS, Qian, ZR & Ogino, S 2017, 'Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells', Oncotarget, vol. 8, no. 50, pp. 87379-87389. https://doi.org/10.18632/oncotarget.20972
Gu, Mancang ; Nishihara, Reiko ; Chen, Yang ; Li, Wanwan ; Shi, Yan ; Masugi, Yohei ; Hamada, Tsuyoshi ; Kosumi, Keisuke ; Liu, Li ; da Silva, Annacarolina ; Nowak, Jonathan A. ; Twombly, Tyler ; Du, Chunxia ; Koh, Hideo ; Li, Wenbin ; Meyerhardt, Jeffrey A. ; Wolpin, Brian M. ; Giannakis, Marios ; Aguirre, Andrew J. ; Bass, Adam J. ; Drew, David A. ; Chan, Andrew T. ; Fuchs, Charles S. ; Qian, Zhi Rong ; Ogino, Shuji. / Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells. In: Oncotarget. 2017 ; Vol. 8, No. 50. pp. 87379-87389.
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AU - Gu, Mancang

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AU - Shi, Yan

AU - Masugi, Yohei

AU - Hamada, Tsuyoshi

AU - Kosumi, Keisuke

AU - Liu, Li

AU - da Silva, Annacarolina

AU - Nowak, Jonathan A.

AU - Twombly, Tyler

AU - Du, Chunxia

AU - Koh, Hideo

AU - Li, Wenbin

AU - Meyerhardt, Jeffrey A.

AU - Wolpin, Brian M.

AU - Giannakis, Marios

AU - Aguirre, Andrew J.

AU - Bass, Adam J.

AU - Drew, David A.

AU - Chan, Andrew T.

AU - Fuchs, Charles S.

AU - Qian, Zhi Rong

AU - Ogino, Shuji

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