Nuclear factor-kappa B inhibition can enhance therapeutic efficacy of 131I on the in vivo management of differentiated thyroid cancer

Meng, Zhen; Lou, Shanshan; Tan, Jian; Xu, Ke; Jia, Qiang; Zheng, Wei; Wang, Shen

doi:10.1016/j.lfs.2012.09.026

Cited by 10 publications

(6 citation statements)

References 57 publications

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“…The apparent discrepancy between our current findings and previously published studies of docetaxel [ 19 ] and I 131 [ 20 , 21 ] is likely explained by the differences in the methodology of establishing the synergistic effect. True synergy occurs when the result of the combination treatment exceeds that of the sum of the effects of each individual treatment and this has to be proven quantitatively.…”

Section: Discussioncontrasting

confidence: 99%

“…A synergistic effect of docetaxel and the NF-κB pathway inhibitor curcumin on the proliferation and apoptosis of the ATC cell line 8505C has been reported [ 19 ]. The combination of the I 131 and NF-κB inhibition with either an IκB kinase (IKK) inhibitor Bay 11–7082 or p65 siRNA resulted in a greater decrease of thyroid cancer growth in vitro [ 20 ] and in a flank xenograft model in mice [ 21 ] than either therapy alone. Encouraged by these findings we designed this study aimed to systematically investigate the benefits of the combination therapy with either docetaxel or ionizing radiation and NF-κB pathway inhibition using in vitro models of thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

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Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer

et al. 2015

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NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα) or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030) inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic approach.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer

et al. 2015

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“…To study the therapeutic potential of the NF-κB inhibitor BAY11-7082 in the treatment of uveal melanoma in vivo , a xenograft nude mouse model with subcutaneous inoculation of OCM1 cells was established [23–24]. After solid tumors were established and palpable, mice were randomly grouped and 1 μM BAY11-7082 was syringed subcutaneously peri-tumor every day for 14 days.…”

Section: Resultsmentioning

confidence: 99%

The Pharmacological NF-κB Inhibitor BAY11-7082 Induces Cell Apoptosis and Inhibits the Migration of Human Uveal Melanoma Cells

Luo

Cun

et al. 2012

IJMS

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Uveal melanomas are highly metastatic and have high rate of recurrence due to the lack of effective systemic therapy. The identification of important survival pathways in uveal melanomas provides novel therapeutic targets for effective treatment. In the present study, we found that the NF-κB signaling pathway was constitutively and highly activated in uveal melanoma cells. Treatment with the pharmacological NF-κB specific inhibitor BAY11-7082 markedly decreased the nuclear translocation of NF-κB. In a dose-dependent setting, BAY11-7082 inhibited the proliferation and growth of uveal melanoma cells by inducing apoptosis without effect on cell cycle. The migration capacity of uveal melanoma cells was also significantly suppressed by BAY11-7082 treatment. Mechanistically, BAY11-7082 increased the activity of caspase 3 and reduced the expression of anti-apoptotic protein Bcl-2, but did not influence the expression of pro-apoptotic protein Bax. Furthermore, BAY11-7082 induced uveal melanoma cell apoptosis and inhibited xenograft tumor growth in vivo. Collectively, the present study identified NF-κB as an important survival signal for uveal melanoma cells and suggested that administration of specific NF-κB inhibitor BAY11-7082 could serve as an effective treatment for patients with uveal melanoma.

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“…Strong correlations between nuclear localization of p65 and clinicopathological parameters of thyroid carcinoma suggested the role of NF-κB activation in tumor growth and aggressiveness [20] . It has also been demonstrated that NF-κB activation induced by chemotherapy or radiotherapy attenuated the therapeutic efficacies [21] , [22] , whereas inhibition of NF-κB signaling could promote thyroid cancer cell apoptosis and achieve synergistic effects [23] , [24] , [25] . Moreover, inhibition of the NF-κB pathway is purported to underlie the anti-tumor effect of melatonin [15] , [26] .…”

Section: Introductionmentioning

confidence: 99%

Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS

Zou

Liu

et al. 2018

Redox Biology

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Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer.

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Nuclear factor-kappa B inhibition can enhance therapeutic efficacy of 131I on the in vivo management of differentiated thyroid cancer

Cited by 10 publications

References 57 publications

Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer

Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer

The Pharmacological NF-κB Inhibitor BAY11-7082 Induces Cell Apoptosis and Inhibits the Migration of Human Uveal Melanoma Cells

Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS

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