Biomedicine & Pharmacotherapy (Jan 2022)

Silencing tumor-intrinsic CD73 enhances the chemosensitivity of NSCLC and potentiates the anti-tumoral effects of cisplatin: An in vitro study

  • Elham Baghbani,
  • Saeed Noorolyai,
  • Shima Rahmani,
  • Dariush Shanehbandi,
  • Mahdi Abdoli Shadbad,
  • Leili Aghebati-Maleki,
  • Ahad Mokhtarzadeh,
  • Oronzo Brunetti,
  • Rossella Fasano,
  • Nicola Silvestris,
  • Behzad Baradaran

Journal volume & issue
Vol. 145
p. 112370

Abstract

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Aims: Besides suppressing anti-tumoral immune responses, tumor-intrinsic inhibitory immune checkpoints have been implicated in tumor development. Herein, we aimed to investigate the significance of tumor-intrinsic CD73, as an inhibitory immune checkpoint, in non-small cell lung cancer (NSCLC) development and propose a novel therapeutic approach. Main methods: We investigated the cell viability, chemosensitivity, apoptosis, migration, and the cell cycle of A-549 and NCI-H1299 following treatment with cisplatin and CD73-small interfering RNA (siRNA) transfection. The 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to study the viability of studied groups and chemosensitivity of tumoral cells. Flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining were used to investigate the apoptosis of NSCLC cells. Flow cytometry and the wound-healing assay were used to investigate the cell cycle and migration of NSCLC cells, respectively. The mRNA expression levels of c-Myc, caspase 3, ROCK, and MMP-9 were investigated to study the underlying molecular mechanism. Key findings: CD73-siRNA transfection has significantly decreased the cell viability and enhanced the chemosensitivity of A-549 and NCI-H1299 cells to cisplatin. CD73-siRNA has considerably stimulated apoptosis, arrested the cell cycle, inhibited tumor migration, downregulated the mRNA expression of c-Myc, MMP-9, and ROCK, and upregulated caspase 3 expression in NSCLC cells. Besides, combined cisplatin therapy with CD73-siRNA transfection has potentiated the aforementioned anti-tumoral effects of cisplatin on NSCLC cells. Significance: Besides suppressing anti-tumoral immune responses, tumor-intrinsic CD73 can facilitate NSCLC development, and the combined cisplatin therapy with CD73-siRNA transfection can substantially enhance the chemosensitivity of NSCLC to cisplatin and potentiates cisplatin-induced anti-tumoral effects on NSCLC.

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