4.5 Article

Nanog suppression enhanced the chemosensitivity of human non-small-cell lung cancer cells to Cisplatin and inhibited cell migration

Journal

PATHOLOGY RESEARCH AND PRACTICE
Volume 233, Issue -, Pages -

Publisher

ELSEVIER GMBH
DOI: 10.1016/j.prp.2022.153869

Keywords

Nanog; Cisplatin; Combination therapy; Non-small-cell lung cancer; Chemosensitivity; Migration

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This study aimed to evaluate the effect of Nanog suppression on the chemosensitivity of lung cancer cells to Cisplatin. The results showed that silencing Nanog significantly increased the sensitivity of lung cancer cells to Cisplatin through apoptosis induction. Additionally, Nanog suppression prevented colony formation and migration abilities of the cancer cells. These findings suggest that silencing Nanog combined with Cisplatin could be a promising treatment approach for lung cancer.
Lung cancer is the leading cause of cancer-associated death in the world. As one of the leading transcription factors in controlling stemness features, Nanog was shown to promote cancer progression, metastasis, and drug resistance. Considering that, this research was conducted to evaluate the effect of Nanog suppression using specific siRNA on the chemosensitivity of lung cancer cells to Cisplatin through inhibition of cell proliferation, migration, and stemness as well as apoptosis induction. Then, A549 lung cancer cells were transfected with Nanog siRNA and treated with Cisplatin individually or combined. Subsequently, to investigate cell proliferation and apoptosis induction, MTT assay and Annexin V/PI staining were performed, respectively. Also, colony formation assay was carried out to evaluate cell stemness features, and migration ability of A549 cells was followed using a wound-healing assay. Gene expression was quantified via qRT-PCR. The obtained results illustrated that siRNA-mediated Nanog suppression remarkably increased the chemosensitivity of A549 cells to Cisplatin through apoptosis induction. Consistently, Nanog suppression combined with Cisplatin led to upregulation of Caspase-3 apoptotic gene and Bax/Bcl-2 ratio. Besides, Nanog knockdown, individually or combined with Cisplatin, prevented colony formation ability of A549 cells by downregulating Sox2 and CD44 genes. It was also indicated that the combination therapy remarkably downregulated MMP9 expression and subsequently suppressed A549 cell migration. A significant reduction was also observed in c-Myc and PD-L1 gene expression levels. In conclusion, the findings of the current study demonstrated that silencing Nanog combined with Cisplatin could be a potent treatment approach for lung cancer patients.

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