In:
Cancer Medicine, Wiley, Vol. 5, No. 4 ( 2016-04), p. 703-710
Abstract:
A 3D microtissues using T47D and JIMT ‐1 cells were generated to analyze tissue‐like response of breast cancer cells after combined human epidermal growth factor receptor 2 ( HER 2)‐targeted treatment and radiation. Following lentiviral knockdown of HER 2, we compared growth rate alterations using 2D monolayers, 3D microtissues, and mouse xenografts. Additionally, to model combined therapeutic strategies, we treated HER 2‐depleted T47D cells and 3D microtissues using trastuzumab (anti‐ HER 2 antibody) in combination with irradiation. Comparison of HER 2 knockdown with corresponding controls revealed growth impairment due to HER 2 knockdown in T47D 2D monolayers, 3D microtissues, and xenografts (after 2, 12, and ≥40 days, respectively). In contrast, HER 2 knockdown was less effective in inhibiting growth of trastuzumab‐resistant JIMT ‐1 cells in vitro and in vivo. Combined administration of trastuzumab and radiation treatment was also analyzed using T47D 3D microtissues. Administration of both, radiation (5 Gy) and trastuzumab, significantly enhanced the growth inhibiting effect in 3D microtissues. To improve the predictive power of potential drugs—as single agents or in combination—here, we show that regarding tumor growth analyses, 3D microtissues are highly comparable to outcomes derived from xenografts. Considering increased limitations for animal experiments on the one hand and strong need of novel drugs on the other hand, it is indispensable to include highly reproducible 3D microtissue platform in preclinical analyses to validate more accurately the capacity of future drug‐combined radiotherapy.
Type of Medium:
Online Resource
ISSN:
2045-7634
,
2045-7634
DOI:
10.1002/cam4.2016.5.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2659751-2
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