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. 2025 Feb;63(1):315-330.
doi: 10.1007/s10528-024-10671-2. Epub 2024 Mar 4.

The Combinatorial Effect of Ad-IL-24 and Ad-HSV-tk/GCV on Tumor Size, Autophagy, and UPR Mechanisms in Multiple Myeloma Mouse Model

Shima Poorghobadi  1 , Seyed Younes Hosseini  2 , Seyed Mehdi Sadat  3 , Asghar Abdoli  3 , Shiva Irani  1 , Kazem Baesi  4
Affiliations

The Combinatorial Effect of Ad-IL-24 and Ad-HSV-tk/GCV on Tumor Size, Autophagy, and UPR Mechanisms in Multiple Myeloma Mouse Model

Shima Poorghobadi et al. Biochem Genet. 2025 Feb.

Abstract

Multiple myeloma is a type of malignant neoplasia whose treatment has changed over the past decade. This study aimed to investigate the effects of combination of Adenovector-carrying interleukin-24 and herpes simplex virus 1 thymidine kinase/ganciclovir on tumor growth, autophagy, and unfolded protein response mechanisms in mouse model of multiple myeloma. Six groups of mice, including Ad-HSV-tk/GCV, Ad-IL-24, Ad-HSV-tk/IL-24, Ad-GFP, and positive and negative controls, were investigated, and each group was injected every 72 h. The tumor size was measured several times. The expression of LC3B evaluated through western blotting and ASK-1, CHOP, Caspase-3, and ATF-6 genes in the UPR and apoptosis pathways were also analyzed by the quantitative polymerase chain reaction (qPCR) method. The present results showed that the injection of Ad-HSV-tk/GCV, Ad-HSV-tk/IL-24, and metformin reduced the tumor size. The expression of LC3B was significantly higher in the treatment groups and positive control groups compared to the negative control group. The expression of CHOP, caspase-3, and ATF-6 genes was significantly higher in the Ad-IL-24 group compared to the other treatment groups. Besides, the ASK-1 expression was significantly lower in the Ad-IL-24 group as compared to the other groups. Overall, the results indicated that the presence of the HSV-tk gene in the adenovectors reduced the size of tumors and induced autophagy by triggering the expression of LC3B protein. The presence of the IL-24 might affect tumor growth but not as much the therapeutic effect of HSV-tk. Furthermore, the results indicated that co-administration of IL-24 and HSV-tk had no synergistic effect on tumor size control.

Keywords: Adenovector; Autophagy; GCV; HSV-tk; IL-24; Multiple myeloma; UPR.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare they have no conflict of interests. Ethical Approval: This research was reviewed by the National Ethics Committee in Biomedical Research and approved under Code of Ethics IR.IAU.SRB.REC.1398.202.

References

    1. Barlogie B, Shaughnessy J, Tricot G, Jacobson J, Zangari M, Anaissie E, Walker R, Crowley J (2004) Treatment of multiple myeloma. Blood 103(1):20–32. https://doi.org/10.1182/blood-2003-04-1045 - DOI - PubMed
    1. B’chir W, Chaveroux C, Carraro V, Averous J, Maurin A-C, Jousse C, Muranishi Y, Parry L, Fafournoux P, Bruhat A (2014) Dual role for CHOP in the crosstalk between autophagy and apoptosis to determine cell fate in response to amino acid deprivation. Cell Signal 26(7):1385–1391. https://doi.org/10.1016/j.cellsig.2014.03.009 - DOI - PubMed
    1. Bhutia SK, Das SK, Azab B, Dash R, Su Z-Z, Lee S-G, Dent P, Curiel DT, Sarkar D, Fisher PB (2011) Autophagy switches to apoptosis in prostate cancer cells infected with melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24). Autophagy 7(9):1076–1077. https://doi.org/10.4161/auto.7.9.16163 - DOI - PubMed - PMC
    1. Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH (2013) Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol 14:1–9. https://doi.org/10.1186/1471-2121-14-32 - DOI
    1. Caparrós E, Francés R (2018) The interleukin-20 cytokine family in liver disease. Front Immunol 9:1155. https://doi.org/10.3389/fimmu.2018.01155 - DOI - PubMed - PMC

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