Your browser doesn't support javascript.
loading
CD13 Induces Autophagy to Promote Hepatocellular Carcinoma Cell Chemoresistance Through the P38/Hsp27/CREB/ATG7 Pathway.
Zhao, Yan; Wu, Huina; Xing, Xiaoyan; Ma, Yuqian; Ji, Shengping; Xu, Xinyue; Zhao, Xin; Wang, Sensen; Jiang, Wenyan; Fang, Chunyan; Zhang, Lei; Yan, Fang; Wang, Xuejian.
Afiliação
  • Zhao Y; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Wu H; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Xing X; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Ma Y; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Ji S; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Xu X; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Zhao X; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Wang S; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Jiang W; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Fang C; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Zhang L; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.).
  • Yan F; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.) yanfang303@wfmc.edu.cn.
  • Wang X; School of Pharmacy, Weifang Medical University, Weifang, Shandong, China (Y.Z., H.W., X.Xi., Y.M., S.J., X.Xu., X.Z., S.W., W.J., C.F., L.Z., F.Y., X.W.) and Department of pharmacy, Southwestern Lu Hospital, Liaocheng, Shandong, China (H.W.) wxj2901@126.com.
J Pharmacol Exp Ther ; 374(3): 512-520, 2020 09.
Article em En | MEDLINE | ID: mdl-32571958
ABSTRACT
The chemoresistance of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutic agents. We previously reported that Aminopeptidase N (CD13) inhibition can enhance the cytotoxic efficacy of chemotherapy agents. In the present study, we use liver cancer cells to explore the molecular mechanism accounting for the relationship between CD13 and chemoresistance. We demonstrate that CD13 overexpression activates the P38/heat shock protein 27/cAMP response element-binding protein (CREB) signaling pathway to limit the efficacy of cytotoxic agents. Moreover, blockade of P38 or CREB sensitizes HCC cells to 5-fluorouracil. Then we reveal that CREB binds to the autophagy related 7 (ATG7) promoter to induce autophagy and promote HCC cell chemoresistance. CD13 inhibition also downregulates the expression of ATG7, autophagy, and tumor cell growth in vivo. Overall, the combination a CD13 inhibitor and chemotherapeutic agents may be a potential strategy for overcoming drug resistance in HCC. SIGNIFICANCE STATEMENT Our study demonstrates that Aminopeptidase N (CD13) promotes hepatocellular carcinoma (HCC) cell chemoresistance via the P38/heat shock protein 27/cAMP response element-binding protein (CREB) pathway. CREB regulates autophagy related 7 transcription and expression to induce autophagy. Our results collectively suggest that CD13 may serve as a potential target for overcoming HCC resistance.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Autofagia / Transdução de Sinais / Carcinoma Hepatocelular / Antígenos CD13 / Resistencia a Medicamentos Antineoplásicos / Neoplasias Hepáticas Limite: Animals / Female / Humans Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Autofagia / Transdução de Sinais / Carcinoma Hepatocelular / Antígenos CD13 / Resistencia a Medicamentos Antineoplásicos / Neoplasias Hepáticas Limite: Animals / Female / Humans Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 2020 Tipo de documento: Article