Adenovirus with p16 gene exerts antitumor effect on laryngeal carcinoma Hep2 cells

Abstract

Laryngeal cancer is an uncommon form of cancer. The tumor suppressor P16, known to be mutated or deleted in various types of human tumor, including laryngeal carcinoma, is involved in the formation and development of laryngeal carcinoma. It has been previously reported that the inactivation or loss of P16 is associated with the acquisition of malignant characteristics. The current study hypothesized that restoring wild‑type P16 activity into P16‑null malignant Hep2 cells may exert an antitumor effect. A recombinant adenovirus carrying the P16 gene (Ad‑P16) was used to infect and express high levels of P16 protein in P16‑null Hep2 cells. Cell proliferation and invasion assays and polymerase chain reaction were performed to evaluate the effects of the P16 gene on cell proliferation and the antitumor effect on Hep2 cells. The results demonstrated that the Hep2 cells infected with Ad‑P16 exhibited significantly reduced cell proliferation, invasion and tumor volume compared with untreated or control adenovirus cells. Furthermore, the expression of laryngeal carcinoma‑associated genes, EGFR, survivin and cyclin D1, were measured in Ad‑P16‑infected cells and were significantly reduced compared with control groups. The results of the current study demonstrate that restoring wild‑type P16 activity into P16-null Hep2 cells exerts an antitumor effect.

p16 loss facilitate hydroquinone‐induced malignant transformation of TK6 cells through promoting cell proliferation and accelerating the cell cycle progression

“…6,18,19 Conversely, p16 expression upregulated in tumor cells promote cell cycle arrest and apoptosis. 20 Tumor suppressor protein p53 is a phosphoprotein that facilitates cellular arrest and apoptosis, and in response to cellular stress helps forbear DNA damage-induced cellular mitosis. 21,22 The mutation of the p53 gene, one of the most common targets for genetic alterations in human cancer, generates defects in the control site of the cell cycle and genetic instability of some tumor cells.…”

The use of adenoviral vectors in gene therapy and vaccine approaches

“…It releases E2F to trigger the cell cycling when it is phosphorylated and P16 , known to be a tumor suppressor gene, prevents pRb phosphorylation and therefore cell cycle progression ( D’Arcangelo et al, 2017 ). P16 is found to be mutated or deleted in different types of cancer ( Yang Z et al, 2016 ) and the restoration of its expression mediated by adenovirus (Ad- P16 ) resulted in antitumor effect in different tumor cell lines with functional pRb protein, but none or reduced activity in cell lines with mutated or null pRb ( Grim et al, 1997 ; Craig et al, 1998 ; Campbell et al, 2000 ) ( Table S2 ). Ad- P16 also increased radiotherapy efficiency in head and neck cancer ( Rhee et al, 2003 ) but conferred chemoresistance to cisplatin and paclitaxel in a P16 -negative bladder cancer cell line ( Grim et al, 1997 ).…”