RESUMO
This publication has been retracted by the Editor due to concerns regarding the originality of the figure images. Reference: Yanting Chai, Ke Xiang, Yezi Wu, Te Zhang, Ying Liu, Xuewen Liu, Weiguo Zhen, Yuan Si. Cucurbitacin B Inhibits the Hippo-YAP Signaling Pathway and Exerts Anticancer Activity in Colorectal Cancer Cells. Med Sci Monit, 2018; 24: LBR9251-9258. DOI: 10.12659/MSM.911594.
RESUMO
BACKGROUND Colorectal carcinoma (CRC) is one of the most frequently diagnosed malignancies. Cucurbitacin B (CuB) is a natural compound isolated from herbs and shows anticancer activity in several cancers. MATERIAL AND METHODS Here, we analyzed the eï¬ects of diï¬erent CuB concentrations on the proliferative and invasive behaviors of CRC cells using MTT, clonogenic assay, Transwell invasion, and wound healing assays. Flow cytometry was performed to measure the apoptotic eï¬ects of CuB on CRC cells. Western blot and real-time PCR were used to investigate the expression of apoptosis and Hippo-YAP signaling pathway proteins. RESULTS CuB inhibited the proliferation and invasion of CRC cells while promoting apoptosis. In addition, the Western blot and real-time PCR results indicated that CuB suppressed YAP expression and its downstream target genes Cyr 61 and c-Myc in CRC cells. To assess the underlying mechanism, we investigated the upstream regulating factor LATS1, and the results revealed that CuB upregulated LATS1 expression in CRC cells. CONCLUSIONS In conclusion, our findings uncovered a novel therapeutic mechanism of CuB and suggest that there is therapeutic potential and feasibility in developing novel YAP inhibitors for cancer treatment.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Fosfoproteínas/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Via de Sinalização Hippo , Humanos , Invasividade Neoplásica/genética , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição , Regulação para Cima , Proteínas de Sinalização YAPRESUMO
The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties. In the present study, we investigated whether PPI can be used in the cisplatin (DDP)-resistant human gastric cancer cell line SGC7901/DDP. The results demonstrated that PPI treatment significantly inhibited cell proliferation, invasion and EMT. TGF-ß1 is known to promote EMT-induced metastasis in numerous tumor types. PPI inhibited the invasion of TGFß1-induced SGC7901/DDP cells in vitro. PPI also increased the mRNA and protein expression levels of E-cadherin but decreased the expression levels of vimentin. Further examination of the mechanism revealed that the CIP2A/PP2A/Akt pathway is partially involved in this regulation of EMT-related biomarkers and invasion. Furthermore, xenograft tests also confirmed the antitumor effects of PPI in vivo. We propose that PPI could be developed as a candidate drug for treating cancer invasion and migration.
Assuntos
Antineoplásicos Fitogênicos , Autoantígenos/genética , Autoantígenos/metabolismo , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Diosgenina/análogos & derivados , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Metástase Neoplásica/genética , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Depressão Química , Diosgenina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Invasividade Neoplásica/prevenção & controle , Fator de Crescimento Transformador beta1/fisiologia , Vimentina/genética , Vimentina/metabolismoRESUMO
BACKGROUND: The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which involves in the progression of several human malignancies. Development of cisplatin (DDP) resistance is the obstacle to an effective control of gastric cancer (GC) clinically. OBJECTIVE: We thus assessed whether CIP2A expression is associated with sensitivity of GC to DDP. METHODS: Real-time quantitative PCR, immunohistochemical analysis, or western blotting was performed to detect CIP2A expression in GC patients' tissues. SGC7901/DDP cells were transfected with CIP2A siRNA. MTT assay was used to determine the DDP-sensitivity of cells. Flow cytometry was used to measure cell apoptosis. RESULTS: CIP2A has higher expression in DDP-resistant GC patients. DDP-resistant GC patients with high CIP2A expression presented with poorer overall survival rates than those with low CIP2A expression. CIP2A knockdown in DDP-resistant GC cells resulted in attenuated proliferative abilities and increased apoptosis level. CIP2A depletion sensitizes DDP-resistant cells to DDP and CIP2A overexpression antagonizes DDP-sensitive cells to DDP. CIP2A influences the expression of multidrug resistance-related proteins in GC cells. CONCLUSIONS: Our results suggested that CIP2A oncoprotein plays an important role in DDP resistance of GC and could serve as a novel therapeutic target for the treatment of GC patients with DDP resistance.
