https://orcid.org/0000-0003-2946-7328
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Abstract
Aim: siRNA can silence targeted genes with lesser toxicity than therapeutic drugs. Therefore, this study aims to investigate new approaches to treat pancreatic cancer (PC) using combinations of siRNA and gemcitabine. Methods: Three genes, ANGTPL4, Notch1 and NF-κβ1, were silenced using siRNA, and their anti-proliferative effects were studied in combination with gemcitabine on pancreatic cancer cell line (PANC-1) using MTT viability assay. Results: Our results showed a significant reduction in PANC-1 cells growth upon treating cells with gemcitabine and single and combinations of siRNA sequences specific for ANGTPL4, Notch1 and NF-κβ1 genes. Conclusion: Co-transfection of gemcitabine-treated PANC-1 cells with ANGPTL4, Notch1 and NF-κβsiRNAs enhances the chemosensitivity of PANC-1 cells to gemcitabine can be a promising therapeutic approach.
Plain language summary
Pancreatic cancer (PC) is prominent with its aggressive behavior and metastatic properties, making it one of the leading causes of cancer-related deaths worldwide. PC is associated with poor prognosis and low survival rate, with 5 years survival rate of less than 9%. Moreover, only 20% of PC patients could undergo surgery, which makes investigating new therapeutic approaches to treat PC necessary. In the current study, the chemosensitivity of pancreatic cancer cells to gemcitabine has been enhanced using a single and combination of ANGTPL4, Notch1 and NF-κβ1 siRNA.
Pancreatic cancer is one of the aggressive cancers, ranking as the fourth most common cause of cancer-related deaths and accounting for 7.5% of all cancer-related deaths worldwide.
Recent studies illustrated the connections between gene-controlling signaling proteins like Notch1, NF-κβ1 and ANGPTL4 and pancreatic tumorigenesis, including metastasis, angiogenesis and proliferation.
Gemcitabine is the first-line chemotherapy for the treatment of pancreatic cancer.
Small interference RNA (siRNA) can be used to silence targeted genes with lesser toxicity than therapeutic drugs and has been used as a targeted therapy to enhance other chemotherapy drug effects against cancer.
The current study reveals for the first time the significant downregulation of the Notch1 gene after silencing the ANGPTL4 gene, which needs further investigation.
Author contributions
A Al-Kadash: carried out the experiments, data curation, software and writing-original draft preparation. W Alshaer: contributed to conceptualization, methodology, investigation, project administration, data validation and writing – original draft. IS Mahmoud: data validation, and writing – editing draft. S Wehaibi: carried out the experiments and data curation. M Zihlif: contributed to supervision, validation and review editing.
Financial disclosure
The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.