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Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma

Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, due to resistance and toxicity, the application of cisplatin for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous study has shown that granulin A (GRN A), an anticancer peptide,...

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Autores principales: Qiao, Gan, Xu, Huanli, Li, Cong, Li, Xiao, Farooqi, Ammad Ahmad, Zhao, Yuming, Liu, Xiaohui, Liu, Ming, Stagos, Dimitrios, Lin, Xiukun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213591/
https://www.ncbi.nlm.nih.gov/pubmed/30301274
http://dx.doi.org/10.3390/ijms19103060
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author Qiao, Gan
Xu, Huanli
Li, Cong
Li, Xiao
Farooqi, Ammad Ahmad
Zhao, Yuming
Liu, Xiaohui
Liu, Ming
Stagos, Dimitrios
Lin, Xiukun
author_facet Qiao, Gan
Xu, Huanli
Li, Cong
Li, Xiao
Farooqi, Ammad Ahmad
Zhao, Yuming
Liu, Xiaohui
Liu, Ming
Stagos, Dimitrios
Lin, Xiukun
author_sort Qiao, Gan
collection PubMed
description Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, due to resistance and toxicity, the application of cisplatin for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous study has shown that granulin A (GRN A), an anticancer peptide, is able to interact with enolase1 (ENO1) and inhibit the growth of HCC in vitro. In the present study, we studied the synergistic effect of the combination of cisplatin and GRN A for the inhibitory effect on HCC. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Chou-Talalay approaches revealed that the combination of GRN A and cisplatin displayed potent synergistic effect. The colony formation and cell viability of HCC cells were inhibited significantly in cells treated with the combination of cisplatin and GRN A, compared with cells treated with cisplatin or GRN A alone. Overexpression of ENO1 diminished the synergistic effect of GRN A and cisplatin in HCC cells. The combination of the two drugs exhibited a more obvious inhibitory effect on cancer cell apoptosis, as analyzed by the cytometry flow, mitochondrial membrane potential (MMP) and western blot analysis. An in vivo study confirmed that the combined use of the two drugs displayed more potent antitumor activity compared to mice treated with cisplatin and GRN A alone; the inhibitory rate of tumor growth was 65.46% and 68.94%, respectively, in mice treated with GRN A and cisplatin. However, the inhibitory rate increased to 86.63% in mice treated with the combination of the two drugs. This study provides evidence that the combination of GRN A and cisplatin is able to sensitize the liver cancer to cisplatin, and that targeting ENO1 is a promising approach for enhancing the antitumor activity of cisplatin.
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spelling pubmed-62135912018-11-14 Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma Qiao, Gan Xu, Huanli Li, Cong Li, Xiao Farooqi, Ammad Ahmad Zhao, Yuming Liu, Xiaohui Liu, Ming Stagos, Dimitrios Lin, Xiukun Int J Mol Sci Article Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, due to resistance and toxicity, the application of cisplatin for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous study has shown that granulin A (GRN A), an anticancer peptide, is able to interact with enolase1 (ENO1) and inhibit the growth of HCC in vitro. In the present study, we studied the synergistic effect of the combination of cisplatin and GRN A for the inhibitory effect on HCC. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Chou-Talalay approaches revealed that the combination of GRN A and cisplatin displayed potent synergistic effect. The colony formation and cell viability of HCC cells were inhibited significantly in cells treated with the combination of cisplatin and GRN A, compared with cells treated with cisplatin or GRN A alone. Overexpression of ENO1 diminished the synergistic effect of GRN A and cisplatin in HCC cells. The combination of the two drugs exhibited a more obvious inhibitory effect on cancer cell apoptosis, as analyzed by the cytometry flow, mitochondrial membrane potential (MMP) and western blot analysis. An in vivo study confirmed that the combined use of the two drugs displayed more potent antitumor activity compared to mice treated with cisplatin and GRN A alone; the inhibitory rate of tumor growth was 65.46% and 68.94%, respectively, in mice treated with GRN A and cisplatin. However, the inhibitory rate increased to 86.63% in mice treated with the combination of the two drugs. This study provides evidence that the combination of GRN A and cisplatin is able to sensitize the liver cancer to cisplatin, and that targeting ENO1 is a promising approach for enhancing the antitumor activity of cisplatin. MDPI 2018-10-07 /pmc/articles/PMC6213591/ /pubmed/30301274 http://dx.doi.org/10.3390/ijms19103060 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Qiao, Gan
Xu, Huanli
Li, Cong
Li, Xiao
Farooqi, Ammad Ahmad
Zhao, Yuming
Liu, Xiaohui
Liu, Ming
Stagos, Dimitrios
Lin, Xiukun
Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma
title Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma
title_full Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma
title_fullStr Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma
title_full_unstemmed Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma
title_short Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma
title_sort granulin a synergizes with cisplatin to inhibit the growth of human hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213591/
https://www.ncbi.nlm.nih.gov/pubmed/30301274
http://dx.doi.org/10.3390/ijms19103060
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