All-trans retinoic acid and cisplatin combined treatment impair motility cell parameters in chemoresistant non-small cell lung cancer (NSCLC) cell lines. Implication of cancer stem cells (CSC)

ANDRES BECHIS; DIEGO BRITEZ NEIRA; LIZETH ARIZA BAREÑO; LUCIANA CAÑONERO; ALDANA SCHEY; ALEJANDRO J. URTREGER; LAURA B. TODARO

Mar del Plata

Congreso; LXVII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

Sociedad Argentina de Investigación Clínica (SAIC)

Cisplatin is a non-small cell lung cancer (NSCLC) standard therapy, although there is a frequent resistance acquisition, where the presence of cancer stem cells (CSC) can be associated with. The Retinoic Acid System has been implicated in the maintenance and expansion of CSC, making it as a potential target therapy.The objective of this work is to evaluate the involvement of all-trans retinoic acid (ATRA) in cell growth modulation in a chemoresistance context, in NSCLC human cell lines. To evaluate that, we have developed two cisplatin-resistant variants from NSCLC cell lines: A549 cell line (A549cpr) and NCI-H125 cell line (H125cpr).Monolayers of parental and cisplatin-resistant cells were treated with ATRA (0.3 - 70μM) and/or Cisplatin for 72h. While the Cisplatin treatment induce growth inhibition, ATRA addition did not modify proliferative capacity. Although all cell lines express all nuclear Retinoic Acid Receptors, the cisplatin-resistant cells showed lower levels of the RARβ/RARγ ratio, indicating a less-differentiate phenotype (p