Resistance of cancer cells to the TRAIL-induced apoptosis in confluent cultures

TRAIL (TNF-alpha Related Apoptosis-Inducing Ligand) is an attractive candidate for anticancer therapy. TRAIL selectively kills tumor cells, without damaging normal cells. It is known that cancer cells can acquire resistance to chemotherapeutic drugs, oxidative stress in high density culture. This phenomenon appears as a multi-cell resistance, cell adhesion-dependent resistance, or density-dependent resistance of tumor cells. However, it is unclear whether such resistance appears in TRAIL-induced apoptosis. We observed that the resistance to izTRAIL of all tumor cell lines used was considerably increased in confluent cultures. The increase in tumor cell resistance in dense populations is not related to their proliferative status. It was shown that the dissociation of calcium-dependent cell-cell contacts with EGTA did not suppress tumor cell resistance to izTRAIL in confluent cultures. This phenomenon of cancer cells resistance to TRAIL-induced apoptosis should be considered in the development of methods of anticancer therapy.