NF-κB signaling plays irreplaceable roles in cisplatin-induced bladder cancer chemoresistance and tumor progression

Sun, Yi; Guan, Zhenfeng; Liang, Liang; Cheng, Yufeng; Zhou, Jiancheng; Li, Jing; Xu, Yan

doi:10.3892/ijo.2015.3256

Cited by 42 publications

(28 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…33, 34 Many anti-apoptotic genes, including Bcl-X L , CIAP2 and livin, have been identified as downstream target genes regulated by NF- κ B signaling. 23, 24, 25 In this study, BST2 was shown to activate the NF- κ B pathway in NPC cells, consistent with previous reports in 293, 293T and HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

Kuang

Hua

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

Concurrent/adjuvant cisplatin-based chemoradiotherapy is regarded as the standard of treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in cisplatin resistance and to clarify their molecular mechanisms, which would help in the discovery of potential therapeutic targets and in developing a personalized and precise treatment approach for NPC patients. We previously generated a cisplatin-sensitive NPC cell line, S16, from CNE2 cells and found that eIF3a, ASNS and MMP19 are upregulated in S16 cells, which contributes to their cisplatin sensitivity. In this study, we found that BST2 is downregulated in cisplatin-sensitive S16 cells compared with CNE2 cells. Knockdown of BST2 in NPC cells sensitized their response to cisplatin and promoted cisplatin-induced apoptosis, whereas exogenous overexpression of BST2 increased their cisplatin resistance and inhibited cisplatin-induced apoptosis. Further investigation demonstrated that BST2-mediated cisplatin resistance depended on the activation of the NF-κB signaling pathway and consequent upregulation of anti-apoptotic genes, such as Bcl-XL and livin. Moreover, an analysis of clinical data revealed that a high BST2 level might serve as an independent indicator of poor prognosis in patients with locally advanced NPC treated with platinum-based chemoradiotherapy. These findings suggest that BST2 likely mediates platinum resistance in NPC, offering guidance for personalized and precise treatment strategies for patients with NPC.

show abstract

Section: Discussionmentioning

confidence: 99%

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

Kuang

Hua

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Platinum-resistant tumor cells usually have a higher threshold for apoptosis induction, mostly due to the overexpression of anti-apoptotic proteins or the defect in mitochondrial signaling. Many factors contribute to these unwanted phenomenons, such as pro-survival signal pathways (Sun et al, 2016;Bao et al, 2017) [i.e., MAPK/ERK (Kong et al, 2015), PI3K/AKT pathway, NF-kB (Miow et al, 2015)], and tumor microenvironment (TME) and epigenetic regulation (Benard et al, 2014;Ramadoss et al, 2017). Researchers begin focusing on the critical role of non-coding RNA in diverse cellular processes; studies demonstrated that non-coding RNA broadly participated in proapoptotic/antiapoptotic proteins regulation and could work as therapeutic targets or predict markers Zarogoulidis et al, 2015).…”

Section: Apoptosismentioning

confidence: 99%

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

et al. 2020

View full text Add to dashboard Cite

Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

show abstract

“…Furthermore, suppression of the process of EMT was found to improve sensitivity to chemotherapeutics in genetically engineered mouse models with deletion of Snail or Twist (12). Research has shown that EMT is induced by activation of the NF-κB signaling pathway, resulting in cisplatin-treatment resistance of bladder cancer (13). Our previous research indicated that the chemotherapy sensitivity of GC cells was enhanced through suppression of the NF-κB signaling pathway following treatment with Ginkgo biloba extract 761 (EGb 761) (14).…”

Section: Introductionmentioning

confidence: 99%

NIK‑ and IKKβ‑binding protein contributes to gastric cancer chemoresistance by promoting epithelial‑mesenchymal transition through the NF‑κB signaling pathway

Liu

Qin

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

Systematic chemotherapy is indispensable for gastric cancer patients with advanced stage disease, but the occurrence of chemoresistance drastically limits treatment effectiveness. There is a tremendous need for identifying the underlying mechanism of chemoresistance. NIK‑ and IKKβ‑binding protein (NIBP) (also known as TRAPPC9, trafficking protein particle complex 9) is a regulator of the cytokine‑induced NF‑κB signaling pathway which has been proven to play pivotal roles in the progression of various malignancies. Nevertheless, it is still ambiguous whether NIBP is involved in the chemoresistance of gastric cancer. The aim of the present study was to investigate the effect of NIBP on chemotherapy resistance of gastric cancer (GC) and to research the mechanisms of Ginkgo biloba extract 761 (EGb 761®) on reversing chemoresistence which has been confirmed in our previous study. In the present study, the results of immumohistochemisty revealed that the positive staining rates of NIBP, NF‑κB p65 and NF‑κB p‑p65 in gastric cancer tissues were obviously higher than those in normal tissues. Furthermore, a close correlation was found to exist between the expression of NIBP and NF‑κB p65 (p‑p65) in gastric cancer tissues. Moreover, the overexpression of NIBP was closely related to tumor differentiation, depth of invasion, clinical stage and lymphatic metastasis in gastric cancer. Western blot analysis, real‑time PCR, MTT assay and flow cytometric analysis were performed and the results demonstrated that compared with the gastric cancer SGC‑7901 cells, the expression of NIBP, NF‑κB p65, NF‑κB p‑p65 and mesenchymal marker vimentin were significantly increased in gastric cancer multidrug‑resistant SGC‑7901/CDDP cells, and the epithelial cell marker ZO‑1 was significantly decreased. Meanwhile, it was found that SGC‑7901/CDDP cells were accompanied by spindle‑like mesenchymal appearance and upregulation of stem cell marker CD133 which has been verified to be an upstream regulatory gene of epithelial‑mesenchymal transition (EMT). Further research confirmed that downregulation of NIBP by Ginkgo biloba extract (EGb) 761 EGb 761 suppressed the cis‑diamminedichloroplatinum(II) (CDDP)‑induced NF‑κB signaling pathway, EMT and the expression of CD133 in SGC‑7901 and SGC‑7901/CDDP cells. Altogether, these data indicate that the NIBP‑regulated NF‑κB signaling pathway plays a pivotal role in the chemoresistance of gastric cancer by promoting CD133‑induced EMT.

show abstract

NF-κB signaling plays irreplaceable roles in cisplatin-induced bladder cancer chemoresistance and tumor progression

Cited by 42 publications

References 25 publications

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

NIK‑ and IKKβ‑binding protein contributes to gastric cancer chemoresistance by promoting epithelial‑mesenchymal transition through the NF‑κB signaling pathway

Contact Info

Product

Resources

About