XIAP Is a Predictor of Cisplatin-Based Chemotherapy Response and Prognosis for Patients with Advanced Head and Neck Cancer

Yang, Xiaopei; Feng, Zhien; Yan, Ming; Hanada, Sayaka; Zuo, Hui; Yang, Chengzhe; Han, Ze-Guan; Guo, Wei; Chen, Wantao; Zhang, Ping

doi:10.1371/journal.pone.0031601

Cited by 67 publications

(53 citation statements)

References 25 publications

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“…XIAP overexpression is important in CDDP resistance in advanced HNC. 22,23 Although our study indicates that XIAP interacts with GSN and that the extent of this interaction and the intracellular trafficking of the complex is differentially regulated by CDDP in chemosensitive and chemoresistant HNC cells, the physiological significance of these findings remains to be determined. However, this finding suggests that GSN acts as a mobile dock for the signaling pathway.…”

Section: Discussionmentioning

confidence: 76%

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Gelsolin regulates cisplatin sensitivity in human head-and-neck cancer

Wang

Abedini

et al. 2014

Int. J. Cancer

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Chemoresistance is a major challenge in cancer therapy. Cisplatin is commonly used for chemotherapy in patients with headand-neck cancer (HNC), but it increases control of the disease by only 10-15%. Downregulation of proapoptotic pathways is a key determinant for chemoresistance in which gelsolin (GSN) is critically involved. We analyzed the association between GSN expression and cisplatin resistance in HNC cell lines, animals with HNC and cancer tissue samples from 58 cisplatin-treated patients with HNC. GSN expression levels were positively associated with chemoresistance in vitro and in vivo. Cisplatin-induced GSN downregulation was associated with the cleavage of GSN and the promotion of apoptosis. GSN silencing facilitated cisplatin-induced apoptosis in chemoresistant cells. In contrast, intact gelsolin was prosurvival in the presence of cisplatin by interacting with X-linked inhibitor of apoptosis protein (XIAP). In chemosensitive cells, cisplatin suppressed GSN-XIAP interaction, promoted translocation of XIAP from the perinuclear region to the nucleus and induced apoptosis. In chemoresistant cells, GSN was highly expressed, and cisplatin had no significant effect on GSN-XIAP interaction and apoptosis. We conclude that GSN is important for chemoresistance in HNC and may be an appropriate therapeutic target in chemoresistant cancers.Although chemotherapy is effective for certain human neoplasms, chemoresistance remains a major hurdle for therapeutic success. Chemoresistance is believed to arise from modified drug targets, altered drug transportation, increased DNA repair or reduced drug-induced macromolecular damage.1 Downregulation of proapoptotic pathways (e.g., Fas,

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Section: Discussionmentioning

confidence: 76%

“…2 XIAP is also important for regulating CDDP sensitivity in head-and-neck cancer (HNC) cells. 9,22,23 In our study, we aimed to define the role of GSN in chemoresistance in HNC, to examine the underlying molecular mechanism involved and to evaluate the possibility of using GSN as a therapeutic target.…”

mentioning

confidence: 99%

Gelsolin regulates cisplatin sensitivity in human head-and-neck cancer

Wang

Abedini

et al. 2014

Int. J. Cancer

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“…Despite extensive efforts, few improvements in treatment have been made in the last 30 years, and the molecular basis of acquired chemoresistance in HNSCC remains largely unknown and continues to be a major complication for chemotherapy (5,6). Clearly, there is an urgent need for understanding mechanisms of therapy resistance and developing more effective novel chemotherapeutic treatment options to improve the survival of HNSCC patients.…”

mentioning

confidence: 99%

Inhibition of HDAC6 Protein Enhances Bortezomib-induced Apoptosis in Head and Neck Squamous Cell Carcinoma (HNSCC) by Reducing Autophagy

Chang

Wang

2016

Journal of Biological Chemistry

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Chemoresistance is a major barrier to effective chemotherapy of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Recently, autophagy, a highly conservative intracellular recycling system, has shown to be associated with chemoresistance in cancer cells. However, little is known about how autophagy plays a role in the development of chemoresistance in HNSCC and how autophagy is initiated when HNSCC cells undergo cytotoxic stress. Here, we report that autophagy was activated when HNSCC cells are treated with the proteasome inhibitor bortezomib, proposed as an alternative chemotherapeutic agent for both primary and cisplatin-resistant HNSCC cells. Ablation of histone deacetylase 6 (HDAC6) expression and its activity in HNSCC cells significantly inhibited autophagy induction by altering the phosphorylation status of mammalian target of rapamycin and enhanced the bortezomib cytotoxicity. Similarly, a combination regimen of bortezomib and the histone deacetylase inhibitor trichostatin A abolished HDAC6 activity and decreased autophagy induction while significantly enhancing bortezomib-induced apoptosis in HNSCC cells. These data uncover a novel molecular mechanism indicating that HDAC6 may serve as a critical causal link between autophagy, apoptosis, and the cell survival response in HNSCC. A combination regimen resulting in regression of autophagy improves chemotherapeutic efficacy, thereby providing a new strategy to overcome chemoresistance and to improve the treatment and survival of HNSCC patients.

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“…It plays a critical role in the inhibition of apoptosis in both death receptor-mediated and mitochondria-mediated pathways [23], [24]. A recent study further demonstrated that XIAP is a predictor of chemotherapy response and prognosis for advanced head and neck cancer patients [25]. Therefore, we also examine the effect of NSC745885 on the XIAP gene and protein expression in oral cancer cells, we treated the SAS cancer cells with different concentrations (0 µM, 0.5 µM, 1.0 µM, 1.5 µM, and 2.0 µM) for 24 hours, and then determined their change in gene expression by using the Q-PCR.…”

Section: Resultsmentioning

confidence: 98%

A Novel Compound NSC745885 Exerts an Anti-Tumor Effect on Tongue Cancer SAS Cells In Vitro and In Vivo

et al. 2014

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ObjectiveOral squamous cell carcinoma (OSCC) is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.MethodsWe investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.ResultsOur results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.ConclusionsThe data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

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XIAP Is a Predictor of Cisplatin-Based Chemotherapy Response and Prognosis for Patients with Advanced Head and Neck Cancer

Cited by 67 publications

References 25 publications

Gelsolin regulates cisplatin sensitivity in human head-and-neck cancer

Gelsolin regulates cisplatin sensitivity in human head-and-neck cancer

Inhibition of HDAC6 Protein Enhances Bortezomib-induced Apoptosis in Head and Neck Squamous Cell Carcinoma (HNSCC) by Reducing Autophagy

A Novel Compound NSC745885 Exerts an Anti-Tumor Effect on Tongue Cancer SAS Cells In Vitro and In Vivo

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