title: Chemoresistance to doxorubicin induces epithelial-mesenchymal transition via upregulation of transforming growth factor β signaling in HCT116 colon cancer cells.
abstract: Doxorubicin (Dox) is a commonly used chemotherapeutic drug in human colon cancer. However, it becomes increasingly ineffective with tumor progression, the underlying mechanism of which remains to be elucidated. Emerging evidence has led to the identification of an association between chemoresistance and the acquisition of epithelial-mesenchymal transition (EMT) in cancer. However, it remains to be elucidated whether this process is involved in the development of resistance to Dox in colon cancer. In HCT116 human colon cancer cells treated with Dox (50 nmol/l), EMT was induced, and transforming growth factor (TGF)β signaling and multi-drug resistant plasma membrane glycoprotein levels were significantly increased. By contrast, silencing of Smad4, using stable RNA interference, inhibited TGFβ signaling, reversed the process of EMT and markedly increased the sensitivity of HCT116 cells to Dox. The results of the present study suggested that the combination of Dox with the downregulation of TGFβ signaling may be a potential novel therapeutic strategy with which to overcome chemoresistance during colon cancer chemotherapy.
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Jinpeng
authors: J
authors: Li
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Hao
authors: H
authors: Liu
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Jieping
authors: J
authors: Yu
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Honggang
authors: H
authors: Yu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051901:Smad4 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D015820:Cadherins; D034741:RNA, Small Interfering; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014746:Vimentin; D004317:Doxorubicin