Imiquimod inhibits the growth of SGC-7901 cells in vitro through induction of autophagy and apoptosis

Jiang, Jiong; Dong, Lei; Shi, Haitao; Guo, Xiaoyan; Qin, Bin; Wang, Yan; Li, Hong

doi:10.3892/mmr.2015.4524

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…Previous studies show that the immunotherapeutic agent imiquimod induces apoptosis in a range of tumour cell lines, including the DFT1 cell line C5065 [15, 16, 30, 34]. To investigate the effects of imiquimod more thoroughly, we analysed DFT1 cell lines (C5065, 1426, 4906) and a DFT2 cell line (RV) after treatment in culture.…”

Section: Resultsmentioning

confidence: 99%

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

et al. 2016

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The survival of the Tasmanian devil (Sarcophilus harrisii) is threatened by devil facial tumour disease (DFTD). This transmissible cancer is usually fatal, and no successful treatments have been developed. In human studies, the small immunomodulatory molecule imiquimod is a successful immunotherapy, activating anti-tumour immunity via stimulation of toll-like receptor-7 (TLR7) signaling pathways. In addition, imiquimod is a potent inducer of apoptosis in human tumour cell lines via TLR7 independent mechanisms. Here we investigate the potential of imiquimod as a DFTD therapy through analysis of treated DFTD cell lines and Tasmanian devil fibroblasts. WST-8 proliferation assays and annexin V apoptosis assays were performed to monitor apoptosis, and changes to the expression of pro- and anti-apoptotic genes were analysed using qRT-PCR. Our results show that DFTD cell lines, but not Tasmanian devil fibroblasts, are sensitive to imiquimod-induced apoptosis in a time and concentration dependent manner. Induction of apoptosis was accompanied by down-regulation of the anti-apoptotic BCL2 and BCLXL genes, and up-regulation of the pro-apoptotic BIM gene. Continuous imiquimod treatment was required for these effects to occur. These results demonstrate that imiquimod can deregulate DFTD cell growth and survival in direct and targeted manner. In vivo, this may increase DFTD vulnerability to imiquimod-induced TLR7-mediated immune responses. Our findings have improved the current knowledge of imiquimod action in tumour cells for application to both DFTD and human cancer therapy.

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Section: Resultsmentioning

confidence: 99%

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

et al. 2016

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“…These apoptotic pathways were activated via mechanisms involving oxidative and endoplasmic reticulum (ER) stress, and regulation of the BCL2 family of proteins [ 14 – 19 ]. Autophagic pathways have also been implicated in this process and may contribute to imiquimod-induced death [ 12 , 13 , 20 ]. In vivo , tumor growth was directly arrested by topical imiquimod treatment in an immune-compromised mouse model of endometrial cancer [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells

et al. 2018

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As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro, but a role for these effects in imiquimod-induced tumor regression remains undefined. We previously demonstrated that cell lines derived from devil facial tumor disease (DFTD), a transmissible cancer threatening the survival of the Tasmanian devil (Sarcophilus harrisii), are sensitive to imiquimod-induced apoptosis. In this study, the pro-apoptotic effects of imiquimod in DFTD have been investigated using RNA-sequencing and label-free quantitative proteomics. This analysis revealed that changes to gene and protein expression in imiquimod treated DFTD cells are consistent with the onset of oxidative and endoplasmic reticulum stress responses, and subsequent activation of the unfolded protein response, autophagy, cell cycle arrest and apoptosis. Imiquimod also regulates the expression of oncogenic pathways, providing a direct mechanism by which this drug may increase tumor susceptibility to immune cytotoxicity in vivo. Our study has provided the first global analysis of imiquimod-induced effects in any tumor cell line. These findings have highlighted the potential of cell stress pathways as therapeutic targets in DFTD, and will allow for improved mechanistic use of imiquimod as a therapy in both the Tasmanian devil and human cancers.

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“…Imikwimod jest agonistą receptora toll-like 7 (TLR 7), za pośrednictwem którego modyfikuje odpowiedź immunologiczną. Ma działanie przeciwnowotworowe i hamujące proliferację komórek, przez mechanizm autofagii, który prowadzi bezpośrednio Dermatology Review/Przegląd Dermatologiczny 2022/5 directly to the induction of apoptosis and tumor cell death [23,24]. Marchitelli et al investigated the efficacy of imiquimod cream in 10 patients with non-invasive vulvar EMPD treated for 5-7 months [25].…”

Section: Opis Przypadkuunclassified

Extramammary Paget disease of the vulva treated with imiquimod

Sadko¹,

Płaszczyńska²,

Czarny³

2022

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Introduction: Extramammary Paget disease of the vulva is a rare, malignant skin neoplasm that typically develops in postmenopausal Caucasian women. Case report: A 70-year-old women reported to the Dermatology Outpatient Clinic with a history of extramammary Paget disease of the vulva, with positive margins after vulvectomy. Considering non-resectability of the lesion, a decision was made to use imiquimod in local therapy on the remaining extramammary Paget disease foci, clinically corresponding to the areas of whitening within the vulva. After 3 months of local therapy, clinical improvement was achieved, and 10 months after the end of treatment, remission was confirmed in histopathological examination based on biopsy. Conclusions: Surgical excision of lesions remains the standard procedure in extramammary Paget disease. Subsequent treatment with imiquimod appears to be beneficial in cases of positive excision margins, to avoid further, mutilating surgery.

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Imiquimod inhibits the growth of SGC-7901 cells in vitro through induction of autophagy and apoptosis

Cited by 8 publications

References 21 publications

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells

Extramammary Paget disease of the vulva treated with imiquimod

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