MicroRNAs expression profile in chemotherapy-induced cardiotoxicity in NSCLC using a co-culture model

Abstract

Clinical application of chemotherapy in lung cancer is constrained by side effects, notably cardiotoxicity, the mechanisms of which remain elusive. This study assessed the potential of specific miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in lung cancer. We employed two lung adenocarcinoma cell lines (Calu6 and H1792) and ventricular normal human cardiac fibroblasts (NHCF-V) in single and co-culture experiments. Functional tests were conducted using 100 µM carboplatin and 1µM vinorelbine doses. The effects of carboplatin and vinorelbine, both individually and in combination, were evaluated at cellular and molecular levels 48h post-therapy for both mono- and co-cultures. miR-205-5p, miR-21-5p, and miR-30a-5p, modulated by anticancer treatments and influencing cardiotoxicity, were analyzed. Vinorelbine and carboplatin treatment promoted apoptosis and autophagy in lung cancer cells and cardiac fibroblasts more than in controls. Western blot analyses revealed BCL2 and p53 protein upregulation. Using qRT-PCR, we investigated the expression dynamics of miR-21-5p, miR-30c-5p, and miR-205-5p in co-cultured cardiomyocytes and lung cancer cells, revealing altered miRNA patterns from vinorelbine and carboplatin treatment. Our findings underscore the intricate relationship between chemotherapy, miRNA regulation, and cardiotoxicity, highlighting the importance of cardiac health in lung cancer treatment decisions.

Vinorelbine Alters lncRNA Expression in Association with EGFR Mutational Status and Potentiates Tumor Progression Depending on NSCLC Cell Lines’ Genetic Profile

“…VRB also induced autophagocytosis and reduced the scratch-healing rate effectively in all cell lines, while further demonstrating variable efficacy across the NSCLC cells. The results here are in line with previous results from our lab and literature [51][52][53]. VRB has been well documented to produce variable effects in cancer therapy, owing to both, the type of tumor and its respective genetic profile, and the administration pattern of the drug [54][55][56].…”