β2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression

Hosseindoost, Saereh; Mousavi, Seyed Mojtaba; Dehpour, Ahmad Reza; Javadi, Seyed Amir Hossein; Arjmand, Babak; Fallah, Ali; Hadjighassem, Mahmoudreza

doi:10.1016/j.omto.2022.05.010

Cited by 4 publications

(6 citation statements)

References 56 publications

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“…Also, reduced Cx43 expression or abnormal gap junction formation has been reported in many tumors (King et al, 2000; Tang et al, 2013). Several chemical substances, such as all‐trans retinoic acid, cAMP, valproic acid, tanshinone IIA, and clenbuterol hydrochloride, have been demonstrated to enhance the killing effect in HSV‐TK/GCV gene therapy via upregulating Cx43 levels and inducing GJIC (Carystinos et al, 1999; Hosseindoost et al, 2022; Ryu et al, 2012; Xiao et al, 2013; Yang et al, 2012). Given that fluoxetine upregulated Cx43 expression in GBM‐derived astrocytes and OECs, we speculate that it may improve the killing effect of gene therapy between cells.…”

Section: Discussionmentioning

confidence: 99%

“…Real‐time PCR was performed as described previously (Hosseindoost et al, 2022). Briefly, total RNA was isolated from the cultured cells using the TRIZol reagent.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as described previously (Hosseindoost et al, 2022). Briefly, cultured cells were lysed using cold RIPA buffer to extract total proteins.…”

Section: Methodsmentioning

confidence: 99%

“…The lentiviral vector particles containing HSV‐TK and GFP were prepared in the previous study (Hosseindoost et al, 2022). In this study, OECs were transduced with the HSV‐TK/GFP vector at an MOI of 50.…”

Section: Methodsmentioning

confidence: 99%

“…The isolation of astrocytes from GBM tumors was performed as in our previous study (Hosseindoost et al, 2022). GBM specimens were obtained from patients whose brain tumor was confirmed as GBM by pathology and resected by a neurosurgeon at Imam Khomeini Hospital, Tehran, Iran.…”

Section: Isolation Of Human Gbm-derived Astrocytementioning

confidence: 99%

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Fluoxetine enhances the antitumor effect of olfactory ensheathing cell‐thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels

Hosseindoost,

Dehpour,

Dehghan

et al. 2023

Drug Development Research

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Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma, resulting in poor clinical outcomes. Herpes simplex virus thymidine kinase/ganciclovir (HSV‐TK/GCV) gene therapy is considered a promising strategy for GBM treatment. Since Connexin43 (Cx43) expression is reduced in GBM cells, increasing Cx43 levels could enhance the effectiveness of gene therapy. The present study aims to examine the impact of fluoxetine on HSV‐TK/GCV gene therapy in human GBM cells using human olfactory ensheathing cells (OECs) as vectors. The effect of fluoxetine on Cx43 levels was assessed using the western blot technique. GBM‐derived astrocytes and OECs‐TK were Cocultured, and the effect of fluoxetine on the Antitumor effect of OEC‐TK/GCV gene therapy was evaluated using MTT assay and flow cytometry. Our results showed that fluoxetine increased Cx43 levels in OECs and GBM cells and augmented the killing effect of OECs‐TK on GBM cells. Western blot data revealed that fluoxetine enhanced the Bax/Bcl2 ratio and the levels of cleaved caspase‐3 in the coculture of OECs‐TK and GBM cells. Moreover, flow cytometry data indicated that fluoxetine increased the percentage of apoptotic cells in the coculture system. This study suggests that fluoxetine, by upregulating Cx43 levels, could strengthen the Antitumor effect of OEC‐TK/GCV gene therapy on GBM cells.

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Section: Discussionmentioning

confidence: 99%

“…Real‐time PCR was performed as described previously (Hosseindoost et al, 2022). Briefly, total RNA was isolated from the cultured cells using the TRIZol reagent.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as described previously (Hosseindoost et al, 2022). Briefly, cultured cells were lysed using cold RIPA buffer to extract total proteins.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Isolation Of Human Gbm-derived Astrocytementioning

confidence: 99%

See 3 more Smart Citations