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Cited by 132Cytokine Signaling Pathways and InteractionsHead and Neck Cancer StudiesEsophageal Cancer Research and Treatment

Stat3 Inhibitor Stattic Exhibits Potent Antitumor Activity and Induces Chemo- and Radio-Sensitivity in Nasopharyngeal Carcinoma

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Pan, Yunbao, Zhou, Fuling, Zhang, Ronghua, Claret, Francois X.·2013·PLoS ONE
DOI 10.1371/journal.pone.0054565PMC PMC3558509
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Abstract

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy most common in East Asia, Africa and Alaska. Radiotherapy and cisplatin-based chemotherapy are the main treatment options. Unfortunately, disease response to concurrent chemoradiotherapy varies among patients with NPC, and many cases are resistant to cisplatin and radiotherapy. Signal transducer and activator of transcription 3 (Stat3) has been implicated in the development and progression of various solid tumors. In this study, we assessed the activation and expression of Stat3 in NPC cells. We found that Stat3 was activated and could be blocked by the small molecule inhibitor Stattic. The inhibition of Stat3 in NPC cells by Stattic decreased the expression of cyclin D1 in a dose- and time-dependent manner. Thus, Stattic was used to target Stat3 in NPC cell lines. We found that Stattic could inhibit cell viability and proliferation in NPC cells and significantly induced apoptosis. Additionally, Stat3 transfection attenuated, whereas Stat3 knockdown enhanced, the effects of Stattic upon cell viability inhibition and apoptosis induction. Furthermore, Stattic sensitized NPC cells to cisplatin and ionizing radiation (IR) by preventing cell proliferation and inducing apoptosis. Taken together, Stattic inhibit Stat3 and display antitumor effect in NPC, and enhanced chemosensitivity and radiosensitivity in NPC. Therefore, our findings provide the base for more rational approaches to treat NPC in the clinic.

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  • Levels of pY-STAT3 are increased in in vitro models and in patients with ionizing radiation-resistant tumors by IR at doses used for radiotherapy (≥2 Gy), contributing to selection of IR-resistant cells in many different cancers.

    “Levels of pY-STAT3 also are increased in in vitro models, as well as in patients with ionizing radiation (IR)–resistant tumors, by IR at doses used for radiotherapy (≥2 Gy), contributing to selection of IR-resistant cells in many different cancers (Ho et al., 2010; Liu et al., 2013; Pan et al., 2013; Yan et al., 2013; Gao et al., 2014; Klein et al., 2014; Lau et al., 2015; Zang et al., 2017; Lu et”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Pan et al., 2013

    The Results section, “Stattic Sensitize NPC Cells to Radiotherapy” (page unavailable), reports that inhibiting STAT3 increased the sensitivity of nasopharyngeal carcinoma cells to 10 Gy irradiation. The paper does not show that irradiation increases pY-STAT3, or establish that such an increase selects resistant cells in patients or across many cancers; its reported increase in STAT3 phosphorylation followed IL-6 treatment, not irradiation. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Pan, Y., Zhou, F., Zhang, R., & Claret, F. X.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Claret, Francois X.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-01-29
Volume
8
Issue
1
Pages
e54565
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0054565
PMC
PMC3558509
OpenAlex
W1979103878
Cited by
132
References
1
Citations by year
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FWCI
7.32
Type
journal article
Language
en
Update notices
correction (2020-08-13)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • China Scholarship Council
  • National Cancer Institute (R01 CA90853, RO1-CA90853, R01CA090853, P30CA016672)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
Keywords
STAT3, Stattic, nasopharyngeal carcinoma, STAT3 inhibitor, cyclin D1, apoptosis, cisplatin sensitivity, radiosensitivity, chemosensitivity, anticancer activity
MeSH terms
Nasopharyngeal Carcinoma, Antineoplastic Agents, Carcinoma, Cell Survival, Cisplatin, Cyclic S-Oxides, Dose-Response Relationship, Drug, Drug Synergism, Humans, Nasopharyngeal Neoplasms, Radiation Tolerance, Radiation-Sensitizing Agents, Time Factors, Signal Transduction, Interleukin-6, Gene Expression, Apoptosis, Drug Resistance, Neoplasm, Cell Line, Tumor, STAT3 Transcription Factor, Cell Cycle Checkpoints

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