FoxM1 mediated resistance to gefitinib in non-smallcell lung cancer cells

Xu, Nuo; Zhang, Xin; Wang, Xun; Ge, Hai Yan; Wang, Xiaoying; Garfield, David H.; Yang, Ping; Song, Yimeng; Bai, Chunxue

doi:10.1038/aps.2011.188

Cited by 39 publications

(27 citation statements)

References 32 publications

(40 reference statements)

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“…recently been reported to be closely related to chemotherapy resistance, and the inhibition of FOXM1 has been shown to increase the sensitivity of tumor cells to chemotherapeutic agents (13,15,(24)(25)(26). We next aimed to ascertain whether combining FOXM1 inhibition with standard chemotherapeutic agents would enhance the effect.…”

Section: Thiostrepton Enhances the Anti-proliferative Effects Of Cispmentioning

confidence: 99%

Inhibition of FOXM1 by thiostrepton sensitizes medulloblastoma to the effects of chemotherapy

et al. 2013

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Abstract. Medulloblastoma (MB) is the most common malignant brain tumor in children and is highly invasive and metastatic. Despite recent advances, most MB patients suffer significant therapy-related morbidity, and the survival rate for patients with metastatic MB remains unsatisfactory. Altered expression of FOXM1 has been detected in many types of cancers, and the inhibition of FOXM1 has been studied as a cancer therapy. In the present study, we evaluated the impact of the inhibition of FOXM1 by thiostrepton in Daoy MB cells. Cells were treated with different concentrations of thiostrepton alone or in combination with cisplatin. Cell viability was measured with CCK-8 assays, and cell cycle distribution and apoptosis were assessed by flow cytometric analysis. Changes in protein expression were examined by western blotting. RNAi experiments were performed using siRNA oligonucleotides. The invasion and migration studies were performed using 8-µm Transwell plates. Inhibition of FOXM1 by thiostrepton significantly decreased MB cell proliferation. Cell arrest at the G2/M phase and apoptosis were significantly increased in MB cell lines that were treated with thiostrepton or transfected with siRNA. Thiostrepton decreased the IC 50 value of cisplatin for MB treatment by enhancing cisplatininduced apoptosis. Thiostrepton also decreased cell invasion and migration, which are crucial steps for tumor progression. Our data suggest that targeting FOXM1 with small-molecule inhibitors results in potent antitumor activity and chemosensitizing effects in human medulloblastoma cells.

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Section: Thiostrepton Enhances the Anti-proliferative Effects Of Cispmentioning

confidence: 99%

Inhibition of FOXM1 by thiostrepton sensitizes medulloblastoma to the effects of chemotherapy

et al. 2013

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“…FoxM1 could induce lung cancer transformation and stimulate tumor cell proliferation (Kim et al, 2006;Wang et al, 2008). It conferred to acquired cisplatin resistance in breast cancer (Kwok, 2010) and primary resistance of gefitinib in non-small cell lung cancer (NSCLC) (Xu et al, 2012 …”

Section: Introductionmentioning

confidence: 99%

Involvement of FoxM1 in Non-Small Cell Lung Cancer Recurrence

Wu²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: Predictive biomarkers for lung cancer recurrence after curative tumor resection remain unclear. This study set out to assess the role of FoxM1 in the recurrence of non-small cell lung cancer. Methods: Immunohistochemistry for FoxM1 expression was performed on paraffin-embedded tumor tissues from 165 NSCLC patients. Association of FoxM1 expression with clinicopathological parameters and disease free survival were evaluated. Results: Our results indicated FoxM1 expression to be significantly associated with poorer tissue differentiation (P =0.03), higher TNM stage (P <0.01), lymph node metastasis (P <0.01), advanced tumor stage (P <0.01), and poorer disease free survival (P <0.01). Multivariable analysis showed that FoxM1 expression increased the hazard of recurrence (hazard ratio= 1.96, 95% CI, 1.04-3.17, P <0.05), indicating that FoxM1 is an independent and significant predictor of lung cancer recurrence. Conclusion: Therefore, FoxM1 is an independent risk factor for recurrence of NSCLC. Elevated FoxM1 expression could be used as an indicator of poor disease free survival.

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“…In addition, FoxM1 mediates the resistance to herceptin and paclitaxel by regulating the tubulin-destabilizing protein stathmin in breast cancer cells [27]. Attenuated FoxM1 expression restored the sensitivity to gefitinib in lung cancer cells by inhibiting proliferation and inducing apoptosis [28]. These results suggest a novel role for FoxM1 in the transcriptional response to DNA damage signaling and the induction of apoptosis, and a potential target for reversing chemoresistance.…”

mentioning

confidence: 83%

FOXM1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and mediates sensitivity to cisplatin in A549 cells via the JNK/mitochondrial pathway

Liu¹,

Chen²,

Gu³

et al. 2015

neo

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The Forkhead box M1 transcription factor (FoxM1) is essential for DNA replication and mitosis, and has important role in cell proliferation and apoptosis. To assess the role of FoxM1 in chemoresistance, we investigated FoxM1 protein expression and the correlation between FoxM1 expression, sensitivity to cisplatin-based therapy, and the survival of non-small cell lung cancer (NSCLC) patients. We generated a cisplatin-resistant lung cancer cell line (A549/CDDP) that showed elevated expression levels of FoxM1 protein and mRNA relative to those of the parental A549 cells. We investigated the effect of the knockdown or overexpression of FoxM1 on the sensitivity to cisplatin and the possible signaling transduction pathways in these cells. Our results revealed that the positive expression rate of FoxM1 in NSCLC was associated with chemosensitivity to cisplatin and a poor prognosis. When the expression of FoxM1 was inhibited by RNA interference, the sensitivity to cisplatin was enhanced. Inversely, in FoxM1-overexpressing cell models, we observed a reduced sensitivity to cisplatin. Moreover, we showed that the downregulation of FoxM1 enhanced cisplatin-induced A549/CDDP cell apoptosis through the activation of the c-Jun NH2-terminal kinase (JNK)/mitochondrial pathway. These results suggest that FoxM1 plays a critical role in chemoresistance to cisplatin and that FoxM1 depletion may be a promising approach to lung cancer therapy.

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FoxM1 mediated resistance to gefitinib in non-smallcell lung cancer cells

Cited by 39 publications

References 32 publications

Inhibition of FOXM1 by thiostrepton sensitizes medulloblastoma to the effects of chemotherapy

Inhibition of FOXM1 by thiostrepton sensitizes medulloblastoma to the effects of chemotherapy

Involvement of FoxM1 in Non-Small Cell Lung Cancer Recurrence

FOXM1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and mediates sensitivity to cisplatin in A549 cells via the JNK/mitochondrial pathway

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