TY - JOUR
T1 - The immunostimulant effects of the rice ragged stunt virus genome on the growth and metastasis of breast cancer in mouse model
AU - Mohammadi, Nejad
AU - Nouri, Fatemeh
AU - Asgari, Yazdan
AU - Moradi-sardareh, Hemen
AU - Sharafi-Kolkeshvandi, Mahnaz
AU - Nemati, Hossein
AU - Kardar, Gholam Ali
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - There are multiple treatment strategies that have been reported for breast cancer, while new and effective therapies against it are still necessary. Stimulating the immune system and its components against cancer cells is one of the unique treatment strategies of immunotherapy and long dsRNAs are immunostimulant in this regard. Based on bioinformatics approaches, a fragment of the Rice ragged stunt RNA virus genome was selected and synthesized according to its immunogenicity. Based on the in vitro transcription technique, dsRNA was synthesized and its binding ability to the PEI/PEI-Ac Polyethylenimine (PEI) or Acetylated polyethylenimine (PEI-Ac) was verified by the gel retardation assay. Then, the PEI-Ac was synthesized by adding acetyl groups to the PEI, and the results of the 1H NMR method indicated its successful synthesis. After cancer induction by 4 T1 cells in Balb/C mice, intraperitoneal (IP) and intratumoral (IT) treatment by the PEI/PEI-Ac-dsRNA were performed and the tumor growth inhibition was evaluated. Results demonstrated that PEI/PEI-Ac-dsRNA can lead to a decrease in tumor weight and volume in both the IP and IT routes. Also, by using macro-metastatic nodule counting and hematoxylin and eosin (H&E) staining we showed that PEI/PEI-Ac-dsRNA can prevent micro and macro-metastasis in the lung. Therefore, the PEI/PEI-Ac-dsRNA acts as an effective inhibitor of growth and metastasis of the breast cancer models. We showed that viral dsRNA can exert its antitumor properties by stimulating TNF-α and IFN-γ. In general, our results revealed that dsRNA derived from the plant virus genome stimulates the intrinsic immune system and can be a potential immune stimulant drug for cancer treatment.
AB - There are multiple treatment strategies that have been reported for breast cancer, while new and effective therapies against it are still necessary. Stimulating the immune system and its components against cancer cells is one of the unique treatment strategies of immunotherapy and long dsRNAs are immunostimulant in this regard. Based on bioinformatics approaches, a fragment of the Rice ragged stunt RNA virus genome was selected and synthesized according to its immunogenicity. Based on the in vitro transcription technique, dsRNA was synthesized and its binding ability to the PEI/PEI-Ac Polyethylenimine (PEI) or Acetylated polyethylenimine (PEI-Ac) was verified by the gel retardation assay. Then, the PEI-Ac was synthesized by adding acetyl groups to the PEI, and the results of the 1H NMR method indicated its successful synthesis. After cancer induction by 4 T1 cells in Balb/C mice, intraperitoneal (IP) and intratumoral (IT) treatment by the PEI/PEI-Ac-dsRNA were performed and the tumor growth inhibition was evaluated. Results demonstrated that PEI/PEI-Ac-dsRNA can lead to a decrease in tumor weight and volume in both the IP and IT routes. Also, by using macro-metastatic nodule counting and hematoxylin and eosin (H&E) staining we showed that PEI/PEI-Ac-dsRNA can prevent micro and macro-metastasis in the lung. Therefore, the PEI/PEI-Ac-dsRNA acts as an effective inhibitor of growth and metastasis of the breast cancer models. We showed that viral dsRNA can exert its antitumor properties by stimulating TNF-α and IFN-γ. In general, our results revealed that dsRNA derived from the plant virus genome stimulates the intrinsic immune system and can be a potential immune stimulant drug for cancer treatment.
KW - Breast cancer
KW - IFN-γ
KW - Immunotherapy
KW - PEI/PEI-Ac nano-carriers
KW - TNF-α
KW - Viral dsRNA
UR - http://www.scopus.com/inward/record.url?scp=85175541595&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2023.111101
DO - 10.1016/j.intimp.2023.111101
M3 - Article
C2 - 37922568
AN - SCOPUS:85175541595
SN - 1567-5769
VL - 125
JO - International Immunopharmacology
JF - International Immunopharmacology
M1 - 111101
ER -