Adipose-Derived Stem Cells Can Replace Fibroblasts as Cell Control for Anti-Tumor Screening Assay

Onco Targets Ther. 2020 Jul 2;13:6417-6423. doi: 10.2147/OTT.S259114. eCollection 2020.

Abstract

Anti-tumor activity screening is a typical process used in anti-tumor drug discovery. The ideal anti-tumor drug candidates are extracts or compounds that can inhibit the proliferation of cancer cells via apoptosis, while exerting minimal effects on normal somatic cells. For a long time, fibroblasts were used as normal cells for all anti-tumor screening assays. However, the fibroblasts exhibited several limitations as cell controls for anti-tumor screening. This study aimed to compare the usage of dermal fibroblasts (DFs) and adipose-derived stem cells (ADSCs) as normal cell controls in anti-tumor screening protocols. The DFs and ADSCs were prepared per the published protocols. The IC50 values of doxorubicin on hepatocellular carcinoma cells HepG2, breast cancer cells MCF-7, DFs and ADSCs were determined via the Alamar blue assay. The side effect indexes (SEIs) were calculated as the ratio of IC50 values of drugs on cancer cells and IC50 values of drugs on DFs, and on ADSCs. The stability of the anti-tumor assay was investigated when carried out on DFs and ADSCs from different passages. The results showed that the IC50 values, as well as SEI values, were not significantly different between using DFs or ADSCs as normal cell controls when DFs and ADSCs were at passage 3. However, for DFs at passage 6 to 12, the IC50 values of doxorubicin were significantly different between DFs and ADSCs. The IC50 values of doxorubicin on DFs were strongly reduced due to the senescence of DFs, while the values were more constant in ADSCs. The SEI values of doxorubicin on DFs, compared to HepG2 and MCF-7 cells, were also changed during passage 3 to 12 of the DFs. However, these values were only slightly changed for ADSCs from the 3rd to 12th passages. ADSCs can replace DFs as a normal cell control for anti-tumor activity screening.

Keywords: adipose-derived stem cell; anti-tumor activity screening; dermal fibroblast; normal cell control.