Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway
Cisplatin (DDP) represents one of the common drugs used for esophageal squamous cell carcinoma (ESCC), but side effects associated with DDP and drug resistance lead to the failure of treatment. This study aimed to understand whether tanshinone IIA (tan IIA) and DDP could generate a synergistic antit...
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doaj-513a26601c1644c5b403eb90e737a9752020-11-25T01:49:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-09-011010.3389/fonc.2020.01756532942Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF PathwayXiaozhong Liao0Xiaozhong Liao1Xiaozhong Liao2Ying Gao3Jiahui Liu4Jiahui Liu5Lanting Tao6Jun Xie7Yueyu Gu8Taoli Liu9Dongmei Wang10Dan Xie11Suilin Mo12Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaThe Second Clinical College, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaCisplatin (DDP) represents one of the common drugs used for esophageal squamous cell carcinoma (ESCC), but side effects associated with DDP and drug resistance lead to the failure of treatment. This study aimed to understand whether tanshinone IIA (tan IIA) and DDP could generate a synergistic antitumor effect on ESCC cells. Tan IIA and DDP are demonstrated to restrain ESCC cell proliferation in a time- and dose-dependent mode. Tan IIA and DDP at a ratio of 2:1 present a synergistic effect on ESCC cells. The combination suppresses cell migration and invasion abilities, arrests the cell cycle, and causes apoptosis in HK and K180 cells. Molecular docking indicates that tan IIA and DDP could be docked into active sites with the tested proteins. In all treated groups, the expression levels of E-cadherin, β-catenin, Bax, cleaved caspase-9, P21, P27, and c-Fos were upregulated, and the expression levels of fibronectin, vimentin, Bcl-2, cyclin D1, p-Akt, p-ERK, p-JNK, P38, COX-2, VEGF, IL-6, NF-κB, and c-Jun proteins were downregulated. Among these, the combination induced the most significant difference. Our results suggest that tan IIA could be a novel treatment for combination therapy for ESCC.https://www.frontiersin.org/article/10.3389/fonc.2020.01756/fullTan IIADDPsynergistic effectESCCNF-κB/COX-2/VEGF pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaozhong Liao Xiaozhong Liao Xiaozhong Liao Ying Gao Jiahui Liu Jiahui Liu Lanting Tao Jun Xie Yueyu Gu Taoli Liu Dongmei Wang Dan Xie Suilin Mo |
spellingShingle |
Xiaozhong Liao Xiaozhong Liao Xiaozhong Liao Ying Gao Jiahui Liu Jiahui Liu Lanting Tao Jun Xie Yueyu Gu Taoli Liu Dongmei Wang Dan Xie Suilin Mo Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway Frontiers in Oncology Tan IIA DDP synergistic effect ESCC NF-κB/COX-2/VEGF pathway |
author_facet |
Xiaozhong Liao Xiaozhong Liao Xiaozhong Liao Ying Gao Jiahui Liu Jiahui Liu Lanting Tao Jun Xie Yueyu Gu Taoli Liu Dongmei Wang Dan Xie Suilin Mo |
author_sort |
Xiaozhong Liao |
title |
Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway |
title_short |
Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway |
title_full |
Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway |
title_fullStr |
Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway |
title_full_unstemmed |
Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway |
title_sort |
combination of tanshinone iia and cisplatin inhibits esophageal cancer by downregulating nf-κb/cox-2/vegf pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-09-01 |
description |
Cisplatin (DDP) represents one of the common drugs used for esophageal squamous cell carcinoma (ESCC), but side effects associated with DDP and drug resistance lead to the failure of treatment. This study aimed to understand whether tanshinone IIA (tan IIA) and DDP could generate a synergistic antitumor effect on ESCC cells. Tan IIA and DDP are demonstrated to restrain ESCC cell proliferation in a time- and dose-dependent mode. Tan IIA and DDP at a ratio of 2:1 present a synergistic effect on ESCC cells. The combination suppresses cell migration and invasion abilities, arrests the cell cycle, and causes apoptosis in HK and K180 cells. Molecular docking indicates that tan IIA and DDP could be docked into active sites with the tested proteins. In all treated groups, the expression levels of E-cadherin, β-catenin, Bax, cleaved caspase-9, P21, P27, and c-Fos were upregulated, and the expression levels of fibronectin, vimentin, Bcl-2, cyclin D1, p-Akt, p-ERK, p-JNK, P38, COX-2, VEGF, IL-6, NF-κB, and c-Jun proteins were downregulated. Among these, the combination induced the most significant difference. Our results suggest that tan IIA could be a novel treatment for combination therapy for ESCC. |
topic |
Tan IIA DDP synergistic effect ESCC NF-κB/COX-2/VEGF pathway |
url |
https://www.frontiersin.org/article/10.3389/fonc.2020.01756/full |
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