Silencing of the transcription factor STAT3 sensitizes lung cancer cells to DNA damaging drugs, but not to TNFα- and NK cytotoxicity

Kulesza, Dorota W.; Carré, Thibault; Chouaı̈b, Salem; Kamińska, Bożena

doi:10.1016/j.yexcr.2012.11.005

Cited by 25 publications

(18 citation statements)

References 45 publications

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“…Previous studies that were mostly performed in vitro, on cultured human cancer cell lines, suggested that STAT3 activation by anthracyclines may mediate chemoresistance, meaning that inhibition of STAT3 enhances the direct cytotoxic effects of DOXO (34)(35)(36)(37). Seemingly corroborating this possibility, we found that anthracycline-based chemotherapy was more efficient against mouse tumor if it was combined with inhibition or deletion of STAT3.…”

Section: Discussionsupporting

confidence: 85%

STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by Stimulating Type 1 Interferon Production by Cancer Cells

et al. 2015

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STAT3 is an oncogenic transcription factor with potent immunosuppressive functions. We found that pharmacologic inhibition of STAT3 or its selective knockout in cancer cells improved the tumor growth-inhibitory efficacy of anthracycline-based chemotherapies. This combined effect of STAT3 inhibition/depletion and anthracyclines was only found in tumors growing on immunocompetent (not in immunodeficient) mice.

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Section: Discussionsupporting

confidence: 85%

STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by Stimulating Type 1 Interferon Production by Cancer Cells

et al. 2015

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“…In NSCLC cells, overexpression of STAT3 mRNA was related with cisplatin-resistance [42,43]. Silencing STAT3 by siRNA led the resistant cells more sensitive to cytotoxic agents such as paclitaxel, doxorubicin and cisplatin [44,45,46]. Secondary, several studies have suggested that the upregulation of STAT3 directly confers a drug-resistant phenotype, such as resistance to ultraviolet radiation-induced apoptosis [32,47].…”

Section: Stat3 In Primary Resistance To Treatmentmentioning

confidence: 99%

The Role of STAT3 in Non-Small Cell Lung Cancer

Harada

Takigawa

Kiura

2014

Cancers

166

148

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Persistent phosphorylation of signal transducer and activator of transcription 3 (STAT3) has been demonstrated in 22%~65% of non-small cell lung cancers (NSCLC). STAT3 activation is mediated by receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and MET, cytokine receptors, such as IL-6, and non-receptor kinases, such as Src. Overexpression of total or phosphorylated STAT3 in resected NSCLC leads to poor prognosis. In a preclinical study, overexpression of STAT3 was correlated with chemoresistance and radioresistance in NSCLC cells. Here, we review the role of STAT3 and the mechanisms of treatment resistance in malignant diseases, especially NSCLC. As STAT3 is a critical mediator of the oncogenic effects of EGFR mutations, we discuss STAT3 pathways in EGFR-mutated NSCLC, referring to mechanisms of EGFR tyrosine kinase inhibitor resistance.

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“…Signal transducer and activator of transcription 3 (Stat3) signaling is constitutively activated and associated with chemoresistance in NSCLC [10]. Inhibition of Stat3 signaling has been documented to sensitize A549 NSCLC cells to DNA damaging drugs doxorubicin and CDDP [11]. Akt signaling is also involved in the chemoresistance of A549 cells to CDDP [12,13].…”

Section: Introductionmentioning

confidence: 99%

Periostin Contributes to Cisplatin Resistance in Human Non-Small Cell Lung Cancer A549 Cells via Activation of Stat3 and Akt and Upregulation of Survivin

Jin

Liu

2016

Cell Physiol Biochem

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Background/Aims: Periostin is upregulated in non-small cell lung cancer (NSCLC). This study was done to explore the function of periostin in the development of cisplatin (CDDP) resistance in NSCLC. Methods: The effects of overexpression or knockdown of periostin on CDDP sensitivity was examined in A549 cells. The involvement of signal transducer and activator of transcription 3 (Stat3) and Akt signaling in the action of periostin was checked. The in vivo effect of periostin silencing on CDDP susceptibility was determined in a mouse xenograft model. Results: Periostin was significantly upregulated in CDDP-resistant A549 cells, compared to parental controls. Overexpression of periostin rendered A549 cells more resistant to CDDP-induced apoptosis and enhanced Stat3 and Akt phosphorylation and survivin expression. Periostin-mediated protection against CDDP-induced apoptosis was compromised by downregulation of survivin. Furthermore, knockdown of periostin re-sensitized CDDP-resistant A549 cells to CDDP. After CDDP treatment, greater volume reduction was observed in periostin-silenced xenograft tumors than in control tumors, which was accompanied by reduced levels of phosphorylated Stat3 and survivin in periostin-depleted tumors. Conclusion: In conclusion, periostin promotes CDDP resistance in NSCLC cells largely through activation of Stat3 and Akt and upregulation of survivin and thus represents a promising target for overcoming CDDP resistance.

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Silencing of the transcription factor STAT3 sensitizes lung cancer cells to DNA damaging drugs, but not to TNFα- and NK cytotoxicity

Cited by 25 publications

References 45 publications

STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by Stimulating Type 1 Interferon Production by Cancer Cells

STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by Stimulating Type 1 Interferon Production by Cancer Cells

The Role of STAT3 in Non-Small Cell Lung Cancer

Periostin Contributes to Cisplatin Resistance in Human Non-Small Cell Lung Cancer A549 Cells via Activation of Stat3 and Akt and Upregulation of Survivin

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