RT Journal Article
SR Electronic
T1 3D Culture Represents Apoptosis Induced by Trastuzumab Better than 2D Monolayer Culture
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2831
OP 2839
VO 38
IS 5
A1 TAKASHI TATARA
A1 TORU MUKOHARA
A1 RINA TANAKA
A1 YOHEI SHIMONO
A1 YOHEI FUNAKOSHI
A1 YOSHINORI IMAMURA
A1 MASANORI TOYODA
A1 NAOMI KIYOTA
A1 MIDORI HIRAI
A1 YOSHIHIRO KAKEJI
A1 HIRONOBU MINAMI
YR 2018
UL http://ar.iiarjournals.org/content/38/5/2831.abstract
AB 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.