3D culture represents apoptosis induced by trastuzumab better than 2D monolayer culture

Takashi Tatara, Toru Mukohara, Rina Tanaka, Yohei Shimono, Yohei Funakoshi, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Midori Hirai, Yoshihiro Kakeji, Hironobu Minami

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Background: Our hypothesis was that three-dimensional (3D) culture better represents differential in vivo responses to trastuzumab between PIK3CA-wild-type (wt) and mutant (mt) cell lines than does two-dimensional (2D) culture. Materials and Methods: Apoptosis and cell signaling proteins were evaluated in response to trastuzumab with and without BKM120, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, using western blot analysis of four breast cancer cell lines with human epidermal growth factor receptor 2 (HER2) amplification. Results: Increased expression of cleaved poly (ADP-ribose) polymerase (PARP) was observed only in 3D-cultured PIK3CA-wt lines in response to trastuzumab, but not in 2D-cultured PIK3CA-wt or PIK3CA-mt lines. Decrease in the ratio of phosphorylated (p-)AKT to AKT in response to trastuzumab was more profound in PIK3CA-wt cells than in PIK3CA-mt cells in 3D culture, while the difference between PIK3CA genotypes was less apparent in 2D culture. Treatment with BKM120 and trastuzumab resulted in a stronger increase in cleaved PARP than either treatment alone. Conclusion: 3D Culture appears to better represent trastuzumab-induced apoptosis and resistance to trastuzumab associated with PIK3CA mutation.

Original languageEnglish
Pages (from-to)2831-2839
Number of pages9
JournalAnticancer research
Issue number5
Publication statusPublished - 05-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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