RESUMO
The authors have requested retraction due to the identification of errors in the data. Reference: Jiafeng Zhang, Xiaojie Jin, Chuan Zhou, Hui Zhao, Ping He, Yalin Hao, Qiongna Dong. Resveratrol Suppresses Human Nasopharyngeal Carcinoma Cell Growth Via Inhibiting Differentiation Antagonizing Non-Protein Coding RNA (DANCR) Expression. Med Sci Monit, 2020; 26: e923622. DOI: 10.12659/MSM.923622.
RESUMO
BACKGROUND Although resveratrol has been found to show anti-cancer effects and potential chemotherapeutic activities in several cancers, the role and molecular mechanisms of resveratrol in nasopharyngeal carcinoma (NPC) remains poorly understood. This study aimed to investigate the effect of resveratrol in NPC progression and its molecular mechanism. MATERIAL AND METHODS Quantitative real-time polymerase chain reaction and western blotting were used to detect the expression of DANCR and PTEN. MTT assay and EdU assay were performed to detect the cell proliferation in NPC cells with different treatment. The effect of resveratrol on cell migration was explored by Transwell migration assay. RNA immunoprecipitation assay and chromatin immunoprecipitation assay were performed to test the interaction between DANCR, EZH2, and PTEN. A mouse xenograft model of NPC cell was established, and immunohistochemistry assay was performed to detect the PTEN expression. RESULTS Resveratrol treatment inhibited NPC cell growth and migration in a dose-dependent manner. Additionally, resveratrol downregulated the expression of DANCR and DANCR overexpressing abrogated the inhibition effect of resveratrol on NPC cell migration. Mechanistically, DANCR could bind to EZH2 and downregulated PTEN expression through mediating the binding of EZH2 on PTEN promoter. Furthermore, rescue experiments suggested resveratrol inhibited NPC cell growth and migration by the DANCR/PTEN pathway. Resveratrol significantly decreased the tumor volume and tumor weight and increased the expression of PTEN. CONCLUSIONS Resveratrol increased PTEN expression and suppressed NPC cell growth and migration through downregulation of DANCR.
Assuntos
Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , RNA Longo não Codificante/antagonistas & inibidores , Resveratrol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Aberrant expression of numerous long noncoding RNAs (lncRNAs) has been reported to be associated with nasopharyngeal carcinoma (NPC). The present study aimed to investigate the expression and function of lncRNA differentiation antagonizing nonprotein coding RNA (DANCR) in NPC pathogenesis. Reverse transcriptionquantitative polymerase chain reaction results suggested that DANCR was significantly upregulated in NPC cells. Overexpression of DANCR promoted 58F cell proliferation and migration, as detected by Cell Counting Kit8, colony formation and wound healing assays. DANCR was additionally identified to inhibit apoptosis, as determined by flow cytometric analysis. Furthermore, DANCR knockdown suppressed cell proliferation and migration, and promoted cell apoptosis in SUNE1 cell. Western blot analysis suggested that DANCR regulated the phosphorylation of AKT serine/threonine kinase and the protein expression of PTEN in NPC cells. Knockdown of DANCR decreased tumor growth in a xenograft model following subcutaneous injection of SUNE1 cells. Collectively, the present results suggested that DANCR regulated the proliferation, migration and apoptosis of NPC cells.
Assuntos
Movimento Celular/genética , Carcinoma Nasofaríngeo/genética , RNA Longo não Codificante/genética , Animais , Apoptose/genética , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Modelos Animais de Doenças , Xenoenxertos , Humanos , Masculino , Camundongos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaio Tumoral de Célula-TroncoRESUMO
Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%-85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.
Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/farmacologia , Neoplasias Colorretais/terapia , Receptores ErbB/genética , Animais , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/imunologia , Feminino , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents used for the treatment of hepatocellular carcinoma (HCC). However, chemoresistance has precluded the use of 5-FU alone in clinical regimens. Combination therapies with 5-FU and other anticancer agents are considered to be a therapeutic option for patients with HCC. We previously reported that the expression of epidermal growth factor receptor variant III (EGFRvIII) can decrease the sensitivity of HCC cells to 5-FU. To overcome this problem, in this study, we elucidated the mechanism underlying EGFRvIII-mediated 5-FU resistance. We observed that EGFRvIII expression can induce miR-520d-3p downregulation and the ensuing upregulation of the transcription factor E2F-1 and the enzyme thymidylate synthase (TS), which may lead to drug resistance. Intriguingly, we found that CH12, a monoclonal antibody directed against EGFRvIII, and 5-FU together had an additive antitumor effect on EGFRvIII-positive HCC xenografts and significantly improved survival in all mice with established tumors when compared with either 5-FU or CH12 alone. Mechanistically, compared with 5-FU alone, the combination more noticeably downregulated EGFR phosphorylation and Akt phosphorylation as well as the expression of the apoptotic protector Bcl-xL and the cell cycle regulator cyclin D1. Additionally, the combination upregulated the expression of the cell cycle inhibitor p27 in in vivo treatment. More interestingly, CH12 treatment upregulated miR-520-3p and downregulated E2F-1 and TS at the mRNA and protein levels. Collectively, these observations suggest that the combination of 5-FU with mAb CH12 is a potential means of circumventing EGFRvIII-mediated 5-FU resistance in HCC.