EGFR inhibitor enhances cisplatin sensitivity of human glioma cells

Zhang, Yan; Xing, Xi-hong; Zhan, Hongfeng; Li, Qiaoyu; Yu, Fan; Zhan, Li; Yu, Qiang; Chen, Jian

doi:10.1007/s11596-011-0675-x

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…Previous findings have confirmed that EGFR and its signaling pathways played an important role in the chemoresistance of cancer cells against CDDP-induced cell apoptosis (21,22). CDDP-resistant cancer cells have altered response to the EGF ligand and enhanced the activation of EGFR (23).…”

Section: Discussionmentioning

confidence: 77%

“…In the present study, we found that after exposure to CDDP, pEGFR expression was significantly increased, suggesting a potential mechanism through which T24 cells demonstrate chemoresistance to CDDP. According to the findings of Zhang et al (21), EGFR-tyrosine kinase inhibitor (AG1478) increased the apoptosis of the human U87 glioma cell line induced by CDDP. Thus, inhibition of the EGFR signaling pathway and reduction of the pEGFR expression may enhance the chemosensitivity of bladder cancer cells to CDDP.…”

Section: Discussionmentioning

confidence: 99%

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Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

et al. 2015

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Abstract. Cisplatin (cis-diaminodichloroplatinum, CDDP) is one of the most effective chemotherapeutic agents that has been widely used in the treatment of many malignancies, including muscle invasive bladder cancer. However, development of CDDP resistance in cancer cells is a major obstacle to the effective treatment of bladder cancer. Therefore, the development of chemosensitizers to overcome the acquired resistance to chemotherapeutic agents is crucial. Previous studies have confirmed that the epidermal growth factor receptor (EGFR) and its signaling pathways are important in the chemoresistance of cancer cells against CDDP-induced cell apoptosis. In a preliminary study we showed that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is the natural ligand of EGFR, and that the extracellular leucine-rich repeat (LRR) domain and immunoglobulin-like domains of LRIG1 were able to bind to the extracellular domain of EGFR, resulting in the downregulation of EGFR expression. Based on these findings, we hypothesized that LRIG1 may enhance the chemosensitivity of bladder cancer cells to CDDP. In the present study, LRIG1 was overexpressed by the adenovirus vector to determine the effect of LRIG1 on chemosensitivity in the T24 bladder cancer cell line and explored the possible mechanisms. The results showed that CDDP inhibited the growth of the T24 cell line and induced activation of EGFR. Overexpression of LRIG1 increased the inhibitory effect of CDDP on the T24 cell line, which may be associated with inactivation of the EGFR signaling pathway, followed by the decrease of Bcl-2 expression and a concomitantly induced expression of Bax. Based on these results, we concluded that the upregulation of LRIG1 expression inhibited the EGFR signaling pathway, activated the mitochondrial pathway of apoptosis and eventually increased the sensitivity of bladder cancer cells to CDDP. IntroductionBladder cancer is the fourth most common malignant disease worldwide, accounting for ~6% of all cancer cases (1). Bladder cancers (75%) are non-muscle-invasive and can be treated by transurethral resection of the bladder tumor combined with intravesical chemotherapeutic agents instillation. However, the prognosis of patients with muscle invasive bladder cancer (25%) remains poor despite the many advances in treatments made over the past few decades. To improve survival rate and extend life span, patients with muscle invasive bladder cancer require chemotherapy after surgery (2). Cisplatin (CDDP)-based chemotherapy is widely used for treatment of muscle invasive bladder cancer (3). However, cancer cell resistance to CDDP is a major obstacle to the effective treatment of bladder cancer, and the underlying mechanism of the resistance is unclear.The molecular mechanisms of CDDP include binding of the drug to DNA and non-DNA targets to form a variety of monoadducts and cross links, which contribute to the cytotoxicity of CDDP by blocking DNA replication and stimulating signals for apoptosis (4). Despite the excellent anticancer effect...

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

et al. 2015

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“…However, its roles and regulatory mechanisms have not yet been fully elucidated. EGFR signaling plays an important role in drug resistance for the treatment of glioblastoma (52) and EGFR inhibitor can enhance cisplatin sensitivity of human glioma cells (52). We demonstrated herein that YY1 expression was increased in cisplatin-resistant U87MG cells and that the silencing of YY1 sensitized the U87MG-cR cells to cisplatin.…”

Section: Discussionmentioning

confidence: 64%

miR-186 reverses cisplatin resistance and inhibits the�formation of the glioblastoma-initiating cell�phenotype by degrading Yin Yang 1 in glioblastoma

Song²,

Guo

2018

Int J Mol Med

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Glioblastoma multiforme (GBM) is among the most devastating types of cancer, with a median survival of <1 year. despite the development of new surgical and radiation techniques, and the use of multiple anti-neoplastic drugs, effective treatment strategies for malignant gliomas have not yet been developed. The limited efficacy of current treatments reflects the resistance of glioblastoma cells to cytotoxic agents. In this study, using western blot analysis, we found that Yin Yang 1 (YY1) expression was increased in cisplatin-resistant glioblastoma U87MG cells (U87MG-cR). We observed that the silencing of YY1 sensitized the U87MG-cR cells to cisplatin and that the overexpression of YY1 promoted the resistance of LN-229 glioblastoma cells to cisplatin, as shown by MTT assay. Using sphere formation assay, we also found that the silencing of YY1 inhibited the formation of the glioblastoma-initiating cell (GIc) phenotype in the U87MG-cR cells. In addition, the results of RT-qPcR revealed that miR-186 expression was decreased in U87MG-CR cells. Using RT-PCR and western blot analysis, we observed that overexpression of miR-186 inhibited YY1 expression in U87MG-CR cells. The overexpression of miR-186 also reversed cisplatin resistance and the formation of the GIc phenotype in glioblastoma cells. On the whole, the findings of this study demonstrate that miR-186 reverses cisplatin resistance and inhibits the formation of the GIc phenotype by degrading YY1 in glioblastoma.

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“…3). Other hub genes, such as EGFR (40), PDGFRA (32), FADD (41) and MET (42) are also associated with cancer. Cancer-related biomarkers are definitely a group or a series of factors.…”

Section: Discussionmentioning

confidence: 99%

A predicted miR-27a-mediated network identifies a signature of glioma

et al. 2012

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The dysregulation of physiological microRNA (miRNA) activity has been shown to play an important role in gliomagenesis. In a previous study, using microRNA arrays and glioma tissues found that miR-27a was upregulated, which was also identified in the glioma cell lines and samples by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, in order to explore the potential roles of miR-27a in the progression of glioma, we first utilized text-mining of PubMed abstracts with natural language processing (NLP) to identify 1,168 glioma-related molecules. In addition, miR-27a targets predicted by computational methods were integrated with the results from NLP analysis, followed by Gene Ontology (GO), pathway and network analysis. We identified 33 hub genes by overlap calculation and demonstrated that miR-27a may be involved in the progression of glioma through adherens junction, focal adhesion, the neurotrophin signaling pathway, the MAPK signaling pathway, the transforming growth factor-β (TGF-β) signaling pathway, cytokine-cytokine receptor interactions, the p53 signaling pathway, the apoptotic signaling pathway, as well as others. Our data may provide researchers with a better understanding of the mechanisms of the miR-27a-target network in glioma initiation and progression.

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EGFR inhibitor enhances cisplatin sensitivity of human glioma cells

Cited by 11 publications

References 34 publications

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

miR-186 reverses cisplatin resistance and inhibits the�formation of the glioblastoma-initiating cell�phenotype by degrading Yin Yang 1 in glioblastoma

A predicted miR-27a-mediated network identifies a signature of glioma

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