Affiliations 

  • 1 Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam 40170, Malaysia
  • 2 Medical Genetics Laboratory, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Seri Kembangan 43400, Malaysia
  • 3 UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Seri Kembangan 43400, Malaysia
Biology (Basel), 2021 Oct 26;10(11).
PMID: 34827096 DOI: 10.3390/biology10111103

Abstract

Pre-clinical studies have demonstrated the efficacy of mesenchymal stem cells (MSCs) expressing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or MSC-TRAIL against several tumors. However, due to the existence of cancer stem cells (CSCs), some tumors, including non-small cell lung cancer (NSCLC), exhibit TRAIL resistance. This study was designed to evaluate the capacity of using first-line chemotherapies including cisplatin, 5-fluorouracil (5-FU) and vinorelbine to act as a chemo-sensitizer on CD133+ (prominin-1 positive) CSCs derived from NSCLC cell lines (A549, H460 and H2170) for the purpose of MSC-TRAIL-induced inhibition. We showed that MSC-TRAIL was resistant to all three chemotherapies compared to the NSCLC cell lines, suggesting that the chemotherapies had little effect on MSC-TRAIL viability. Pre-treatment using either cisplatin or 5-FU, but not with vinorelbine, was able to increase the efficacy of MSC-TRAIL to kill the TRAIL-resistant A549-derived CSCs. The study also demonstrated that both 5-FU and vinorelbine were an effective chemo-sensitizer, used to increase the anti-tumor effect of MSC-TRAIL against H460- and H2170-derived CSCs. Furthermore, pre-treatment using cisplatin was noted to enhance the effect of MSC-TRAIL in H460-derived CSCs; however, this effect was not detected in the H2170-derived CSCs. These findings suggest that a pre-treatment using certain chemotherapies in NSCLC could enhance the anti-tumor effect of MSC-TRAIL to target the CSCs, and therefore the combination of chemotherapies and MSC-TRAIL may serve as a novel approach for the treatment of NSCLC.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.