Enhanced effect of recombinant adenoviruses co-expression of ING4 and OSM on anti-tumour activity of laryngeal cancer

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE(2022)

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Abstract
The inhibitor of growth family member 4 (ING4) is one of the ING family genes, serves as a repressor of angiogenesis or tumour growth and suppresses loss of contact inhibition. Oncostatin M (OSM) is a multifunctional cytokine that belongs to the interleukin (IL)-6 subfamily with several biological activities. However, the role of recombinant adenoviruses co-expressing ING4 and OSM (Ad-ING4-OSM) in anti-tumour activity of laryngeal cancer has not yet been identified. Recombinant Ad-ING4-OSM was used to evaluate their combined effect on enhanced anti-tumour activity in Hep-2 cells of laryngeal cancer in vivo. Moreover, in vitro function assays of co-expression of Ad-ING4-OSM were performed to explore impact of co-expression of Ad-ING4-OSM on biological phenotype of laryngeal cancer cell line, that is Hep-2 cells. In vitro, Ad-ING4-OSM significantly inhibited the growth, enhanced apoptosis, altered cell cycle with G1 and G2/M phase arrest, and upregulated the expression of P21, P27, P53 and downregulated survivin in laryngeal cancer Hep-2 cells. Furthermore, in vivo functional experiments of co-expressing of Ad-ING4-OSM demonstrated that solid tumours in the nude mouse model were significantly suppressed, and the co-expressing Ad-ING4-OSM showed a significant upregulation expression of P21, P53, Bax and Caspase-3 and a downregulation of Cox-2, Bcl-2 and CD34. This study for the first time demonstrated the clinical value and the role of co-expressing Ad-ING4-OSM in biological function of laryngeal cancer. This work suggested that co-expressing Ad-ING4-OSM might serve as a potential therapeutic target for laryngeal cancer patients.
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Key words
gene therapy, growth family member 4, laryngeal cancer, Oncostatin M
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