Targeting the inflammatory pathways to enhance chemotherapy of cancer

Zhu, Zhaowei; Zhong, Shan; Zhang, Shen

doi:10.4161/cbt.12.2.15952

Cited by 46 publications

(27 citation statements)

References 151 publications

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“…In the present study, we found a new mechanism that activation of FXR-SHP pathway could significantly induce dephosphorylation of STAT3 and inhibit expression of its target Bcl-xL. Activated STAT signaling in human tumors provide novel molecular targets for therapeutic intervention [22, 36]. Previous studies have found that IL-6/STAT3 signaling is aberrant in human CC cells and CC tissues, with prolonged and sustained STAT-3 phosphorylation [23, 24].…”

Section: Discussionmentioning

confidence: 72%

FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression

Wang

Zhan

et al. 2016

Oncotarget

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Chemoresistance is common in patients with biliary tract cancer (BTC) including gallbladder cancer (GBC) and cholangiocarcinoma (CC). Therefore, it is necessary to identify effective chemotherapeutic agents for BTC. In the present study, we for the first time tested the effect of farnesoid X receptor (FXR) agonists GW4064 and CDCA (chenodeoxycholic acid) in combination with cisplatin (CDDP) on increasing the chemosensitivity in BTC. Our results show that co-treatment of CDDP with FXR agonists remarkably enhance chemosensitivity of BTC cells. Mechanistically, we found that activation of FXR induced expression of small heterodimer partner (SHP), which in turn inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation and resulted in down-regulation of Bcl-xL expression in BTC cells, leading to increased susceptibility to CDDP. Moreover, the experiments on tumor-bearing mice showed that GW4064/CDDP co-treatment inhibited the tumor growth in vivo by up-regulating SHP expression and down-regulating STAT3 phosphorylation. These results suggest CDDP in combination with FXR agonists could be a potential new therapeutic strategy for BTC.

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Section: Discussionmentioning

confidence: 72%

FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression

Wang

Zhan

et al. 2016

Oncotarget

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“…Both in vitro and in vivo studies have shown that targeted NF-κB inhibition sensitized tumor cells to chemotherapy and radiation. However, targeting NF-κB in solid tumors did not achieve optimal treatment outcomes [17]. This may be explained by the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment

Han

Wang

et al. 2016

Oncotarget

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Hypoxia is a prominent feature of the microenvironment of solid tumors and may contribute to tumor progression through the oxygen-sensitive transcriptional regulator hypoxia-inducible factor-1 (HIF-1). Chronic inflammation is another typical feature. Inflammatory mediators, including Toll-like receptors (TLRs) and nuclear factor-κB (NF-κB), play an important role in cancer development. Recent studies have revealed extensive cross-talk between hypoxia and inflammation signaling, though the mechanisms remain unclear. Our results confirm that TLR3 and TLR4 are highly expressed in oral squamous cell carcinoma (OSCC). Activation of TLR3 and TLR4 stimulated the expression of HIF-1 through NF-κB. In addition, HIF-1 increased the expression of TLR3 and TLR4 through direct promoter binding. Thus, the TLR/NF-κB pathway forms a positive feedback loop with HIF-1. These results indicate a novel cross-talk between the TLR/NF-κB and HIF-1 signaling, which may contribute to OSCC initiation and progression. With the elucidation of this novel mechanism, it might serve as a basis for future microenvironment targeted cancer therapy.

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“…As a result, the last few years have seen a shift away from drugs designed to inhibit oncogenic drivers of cancer and toward agents that can block factors enabling the growth and/or survival of tumor cells. The targeting of tumor angiogenesis (34,35), inflammation (36,37), and immune evasion (38) are all receiving increasing attention in this respect. The metabolic adaptations displayed by cancer cells are also being viewed with fresh eyes and evaluated for their potential as drug targets.…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

Molecular Pathways: Tumor Cells Co-opt the Brain-Specific Metabolism GeneCPT1Cto Promote Survival

Reilly

Mak

2012

Clinical Cancer Research

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The metabolic adaptations of cancer cells are receiving renewed attention as potential targets for therapeutic exploitation. Recent work has highlighted the importance of fatty acid catabolism through b-oxidation to cellular energy homeostasis. In this article, we describe recent preclinical studies suggesting that a gene usually expressed only in the brain, carnitine palmitoyltransferase (CPT)1C, promotes cancer cell survival and tumor growth. CTP1C confers rapamycin resistance on breast cancer cells, indicating that this gene may act in a pathway parallel to mTOR-enhanced glycolysis. Because of CPT1C's normally brainrestricted expression and the inability of most drugs to pass the blood-brain barrier, CPT1C may be an ideal candidate for specific small-molecule inhibition. We further speculate that concurrent targeting of CPT1C activity and glycolysis in tumor cells could be a highly effective anticancer approach.

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Targeting the inflammatory pathways to enhance chemotherapy of cancer

Cited by 46 publications

References 151 publications

FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression

FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression

Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment

Molecular Pathways: Tumor Cells Co-opt the Brain-Specific Metabolism GeneCPT1Cto Promote Survival

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