Open Access

Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer

  • Authors:
    • Tomoya Kato
    • Mikihito Nakamori
    • Shuichi Matsumura
    • Masaki Nakamura
    • Toshiyasu Ojima
    • Hiroshi Fukuhara
    • Yasushi Ino
    • Tomoki Todo
    • Hiroki Yamaue
  • View Affiliations

  • Published online on: April 23, 2021     https://doi.org/10.3892/ol.2021.12751
  • Article Number: 490
  • Copyright: © Kato et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Currently, gastric cancer is the third most common cause of cancer‑associated mortality worldwide. Oncolytic virotherapy using herpes simplex virus (HSV) has emerged as a novel therapeutic strategy against cancer. Telomerase is activated in >90of malignant tumors, including gastric cancer, and human telomerase reverse transcriptase (hTERT) is one of the major components of telomerase enzyme. Therefore, in oncolytic HSV, placing the essential genes under the regulation of the hTERT promoter may enhance its antitumor efficacy. The present study examined the antitumor effect of fourth‑generation oncolytic HSVs, which contain the ICP6 gene under the regulation of the hTERT promoter (T‑hTERT). To examine the association between hTERT expression and prognosis in patients with gastric cancer, immunohistochemical analysis of resected tumor specimens was performed. The enhanced efficacy of T‑hTERT was determined in human gastric cancer cell lines in vitro and in human gastric adenocarcinoma specimens in vivo. In in vitro experiments, enhanced cytotoxicity of T‑hTERT was observed in MKN1, MKN28 and MKN45 cells compared with that of a third‑generation oncolytic HSV, T‑null. In particular, the cytotoxicity of T‑hTERT was markedly enhanced in MKN45 cells. Furthermore, in vivo experiments demonstrated that 36.7 and 54.9% of cells were found to be lysed 48 h after infection with T‑null or T‑hTERT viruses at 0.01 pfu/cell, respectively. The T‑hTERT‑treated group exhibited considerably lower cell viability than the control [phosphate‑buffered saline (‑)] group. Therefore, employing oncolytic HSVs that contain the ICP6 gene under the regulation of the hTERT promoter may be an effective therapeutic strategy for gastric cancer. To the best of our knowledge, the present study was the first to describe the effect of an oncolytic HSV with ICP6 expression regulated by the hTERT promoter on gastric cancer cells.
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June-2021
Volume 21 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Kato T, Nakamori M, Matsumura S, Nakamura M, Ojima T, Fukuhara H, Ino Y, Todo T and Yamaue H: Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer. Oncol Lett 21: 490, 2021
APA
Kato, T., Nakamori, M., Matsumura, S., Nakamura, M., Ojima, T., Fukuhara, H. ... Yamaue, H. (2021). Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer. Oncology Letters, 21, 490. https://doi.org/10.3892/ol.2021.12751
MLA
Kato, T., Nakamori, M., Matsumura, S., Nakamura, M., Ojima, T., Fukuhara, H., Ino, Y., Todo, T., Yamaue, H."Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer". Oncology Letters 21.6 (2021): 490.
Chicago
Kato, T., Nakamori, M., Matsumura, S., Nakamura, M., Ojima, T., Fukuhara, H., Ino, Y., Todo, T., Yamaue, H."Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer". Oncology Letters 21, no. 6 (2021): 490. https://doi.org/10.3892/ol.2021.12751