Sartorius eBook - 40

THE FUTURE OF DRUG DISCOVERY: LIVE 3D CELL ANALYSIS

Lapitinib (10 μM)

CMP (10 μM)

SK-BR-3 + NHDF

MCF7 + NHDF

Control

Figure 5: Interrogation of images to gain greater insight. MCF7 or SK-BR-3 cells co-cultured with NHDFs were seeded in pre-coated
(Matrigel) flat bottom 96-well plates (1:1 ratio, 1,000 cells/well of each) and multi-spheroids allowed to form (3 d) prior to treatment
with Lapatinib and Camptothecin (CMP). Incucyte® Brightfield images (5 d) show the effects of treatments on multi-spheroid size and
integrity. Note: cytotoxic effects of CMP on both MCF7 and SK-BR-3 multi-spheroids and their difference in sensitivity to Lapatinib.

by Lapatinib and ZK164015 aligned with the

Herceptin®-Induced ADCC in

known expression profile of receptors targeted

HER2-Positive Multi-Spheroids

by these agents3. The dual EGRF and HER2

The regulation of immune-mediated killing

tyrosine kinase inhibitor, Lapatinib, caused a

by mono-clonal antibodies is an important

concentration-dependent inhibition of SK-BR-3

mechanism of action in immunotherapy

and BT-474 multi-spheroid growth, while the

treatments4. Binding of antibodies such as

estrogen receptor (ER) antagonist ZK164015

Herceptin (a humanized monoclonal antibody

was a potent inhibitor of MCF7 multi-spheroid

targeting HER2 receptor) to receptors induces

growth. ZK164015 had little or no effect on

antibody-dependent, cell-mediated cytotoxicity

multi-spheroids devoid of ER expression. The

(ADCC).

DNA topoisomerase inhibitor, CMP, caused

The impact of Herceptin-induced ADCC was

comparable inhibition of growth across all multi-

evaluated in HER2-positive (SKOV3 and BT474)

spheroids types.

and HER2-negative (MCF7) multi-spheroids.

40 |

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