Secreted amphiregulin promotes vincristine resistance in oral squamous cell carcinoma
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Le résumé fourni par la source
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. Despite advances in surgery, radiotherapy and chemotherapy, the overall 5‑year survival rate of patients with OSCC has not significantly improved. In addition, the prognosis of patients with advanced‑stage OSCC remains poor. Therefore, it is necessary to develop novel therapeutic modalities. Vincristine (VCR), a naturally occurring vinca alkaloid, is a classical microtubule‑destabilizing agent and is widely used in the treatment of a number of cancers. Despite the proven antitumor benefits of VCR treatment, one of the major reasons for the failure of treatment is drug resistance. Changes in the tumor microenvironment are responsible for cross‑talk between cells, which may facilitate drug resistance in cancers; secreted proteins may promote communication between cancer cells to induce the development of resistance. To identify the secreted proteins involved in VCR resistance, conditioned media was obtained, and an antibody array was conducted to screen a comprehensive secretion profile between VCR‑resistant (SAS‑VCR) and parental (SAS) OSCC cell lines. The results showed that amphiregulin (AREG) was highly expressed and secreted in SAS‑VCR cells. Pretreatment with exogenous recombinant AREG markedly increased drug resistance against VCR in OSCC cells, as assessed by an MTT assay. Colony formation, MTT and western blot assays were performed to investigate the effects of AREG knockdown on VCR sensitivity. The results indicated that AREG expression can regulate VCR resistance in OSCC cells; overexpression of AREG increased VCR resistance in parental cells, whereas AREG knockdown decreased the VCR resistance of resistant cells. In addition, it was also demonstrated that the glycogen synthase kinase‑3β pathway may be involved in AREG‑induced VCR resistance. These findings may provide rationale to combine VCR with blockade of AREG‑related pathways for the effective treatment of OSCC.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Secreted amphiregulin promotes vincristine resistance in oral squamous cell carcinoma
- Date Crossref
- 30/08/2019
- Éditeur
- Spandidos Publications
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Changhua Christian Hospital pays non établi dans la noticeÉtablissement de santé
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Chiayi Chang Gung Memorial Hospital Department of Medical Research pays non établi dans la noticeÉtablissement de santé
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National Yang Ming Chiao Tung University pays non établi dans la noticeUniversité ou école supérieure
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National Taiwan University of Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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China Medical University pays non établi dans la noticeUniversité ou école supérieure
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National Chiayi University Department of Biochemical Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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Oral Cancer Research Center pays non établi dans la noticeStructure de recherche
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Department of Otorhinolaryngology‑Head and Neck Surgery pays non établi dans la noticeOrganisation à but non lucratif
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National Yang‑Ming University Department of Biotechnology and Laboratory Science in Medicine pays non établi dans la noticeUniversité ou école supérieure
Changhua Christian Hospital, Department of Medical Research — Chiayi Chang Gung Memorial Hospital et National Yang Ming Chiao Tung University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.