A new drug testing platform based on 3D tri-culture in lab-on-a-chip devices

Gokce B., Akcok I., Cagir A., Pesen-Okvur D.

European Journal of Pharmaceutical Sciences, vol.155, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 155
  • Publication Date: 2020
  • Doi Number: 10.1016/j.ejps.2020.105542
  • Journal Name: European Journal of Pharmaceutical Sciences
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Drug discovery, Breast cancer cell, 3D cell culture, Tri-culture, doxorubicin, (R)-4 '-methylklavuzon, Lab-on-a-chip, CELL-CULTURE, CANCER-CELLS, TUMOR-CELLS, DOXORUBICIN, COCULTURE, APOPTOSIS, 2D, THERAPEUTICS, FIBROBLASTS, ADRIAMYCIN
  • Abdullah Gül University Affiliated: Yes


© 2020 Elsevier B.V.Drug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4′-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.