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<p>Improving immune cell functions in tumors remains a main challenge in cancer immunotherapy. NK are main innate effector cells with anti-tumor activity against various tumors. Consequently, NK cells are proper candidates for cancer immunotherapy, including gastric cancer. The IL-15 signaling pathway is negatively regulated by a protein called <i>Cish encoded</i> by the <i>Cish</i> gene. In the present study, we explored the knockdown of <i>Cish</i> and anti-tumor effects of NK cells. We knockdown <i>Cish</i> in human primary NK cells using siRNA, and the expression of <i>Cish</i> was evaluated by qRT-PCR. Gene expression analysis revealed that <i>Cish</i> expression increased after induction by IL-15 at various time point and conversely decreased after knockdown, approximately 44% and 41% reduction were observed at siRNA concentrations of 100 nmol/l at timepoint of 6h and 48h, respectively. <i>Cish</i> knockdown of human NK cells, showed enhanced the anti-tumor effects and induced apoptosis against a human gastric cancer cell lines called MKN-45 and AGS. Additionally, co-culture with MKN-45 and AGS cells showed increased secretion of IFN-γ and TNF-ɑ that could be related to higher cytotoxicity of knockdown <i>Cish</i> NK cells. Our results indicate that <i>Cish</i> knockdown human NK cells enhanced cytotoxicity and cytokine production when co-cultured with gastric cancer cell lines. siRNA-mediated <i>Cish</i> knockdown NK cells, might be a promising immunotherapeutic alternative in patients with gastric cancer.</p>

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Reduced Cish expression by siRNA knockdown in Natural Killer cells promotes anti-tumor effects against gastric cancer cell lines

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月4日

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  • Sahar Khojastehpour,
  • Azarmidokht Aminazad,
  • Shahrokh Abdolahi,
  • Shirin Tavakoli,
  • Maryam Samareh-Salavati,
  • Nasrin Momeni,
  • Mohammad Vaezi,
  • Mohammad Ahmadvand

摘要

Improving immune cell functions in tumors remains a main challenge in cancer immunotherapy. NK are main innate effector cells with anti-tumor activity against various tumors. Consequently, NK cells are proper candidates for cancer immunotherapy, including gastric cancer. The IL-15 signaling pathway is negatively regulated by a protein called Cish encoded by the Cish gene. In the present study, we explored the knockdown of Cish and anti-tumor effects of NK cells. We knockdown Cish in human primary NK cells using siRNA, and the expression of Cish was evaluated by qRT-PCR. Gene expression analysis revealed that Cish expression increased after induction by IL-15 at various time point and conversely decreased after knockdown, approximately 44% and 41% reduction were observed at siRNA concentrations of 100 nmol/l at timepoint of 6h and 48h, respectively. Cish knockdown of human NK cells, showed enhanced the anti-tumor effects and induced apoptosis against a human gastric cancer cell lines called MKN-45 and AGS. Additionally, co-culture with MKN-45 and AGS cells showed increased secretion of IFN-γ and TNF-ɑ that could be related to higher cytotoxicity of knockdown Cish NK cells. Our results indicate that Cish knockdown human NK cells enhanced cytotoxicity and cytokine production when co-cultured with gastric cancer cell lines. siRNA-mediated Cish knockdown NK cells, might be a promising immunotherapeutic alternative in patients with gastric cancer.