Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. More than 30% of patients with diagnosed HCC have abnormally high expression of fibroblast growth factor receptor 4 (FGFR4). Currently, clinical trials for a variety of FGFR4-specific inhibitors have started. However,...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.1087656/full |
| _version_ | 1798014858136911872 |
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| author | Qi Wang Juan Liu Juan Liu Wenzhen Yin Dawei Sun Zhongsong Man Shangwei Jiang Xiufeng Ran Yuxin Su Yunfang Wang Yunfang Wang Yunfang Wang Jiahong Dong Jiahong Dong Jiahong Dong |
| author_facet | Qi Wang Juan Liu Juan Liu Wenzhen Yin Dawei Sun Zhongsong Man Shangwei Jiang Xiufeng Ran Yuxin Su Yunfang Wang Yunfang Wang Yunfang Wang Jiahong Dong Jiahong Dong Jiahong Dong |
| author_sort | Qi Wang |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. More than 30% of patients with diagnosed HCC have abnormally high expression of fibroblast growth factor receptor 4 (FGFR4). Currently, clinical trials for a variety of FGFR4-specific inhibitors have started. However, the effect of these inhibitors is not ideal, and it is necessary to find a drug combination to synergistically exert anti-tumor effects. We found strong correlations between FGFR4 and HCC clinicopathological characteristics in the present study. After grouping patients according to FGFR4 expression, the key gene signatures were inputted the drug-gene related databases, which predicted several potential drug candidates. More importantly, to achieve the reliable and high throughput drug cytotoxicity assessment, we developed an efficient and reproducible agarose hydrogel microwells to generate uniform-sized multicellular tumor spheroids, which provide better mimicry of conventional solid tumors that can precisely represent anticancer drug candidates’ effects. Using high content screening, we quickly evaluated the enhanced anti-tumor effects of these combinations. Finally, we demonstrated that Parthenolide is a potential drug that can significantly enhance the clinical efficacy of FGFR4 receptor inhibitors. In general, we offered a new therapeutic way for FGFR4 positive HCC patients. |
| first_indexed | 2024-04-11T15:23:48Z |
| format | Article |
| id | doaj.art-a5d1e2c4f8604b46a3510e1a67f8a7d2 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-11T15:23:48Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-a5d1e2c4f8604b46a3510e1a67f8a7d22022-12-22T04:16:18ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-12-011010.3389/fbioe.2022.10876561087656Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinomaQi Wang0Juan Liu1Juan Liu2Wenzhen Yin3Dawei Sun4Zhongsong Man5Shangwei Jiang6Xiufeng Ran7Yuxin Su8Yunfang Wang9Yunfang Wang10Yunfang Wang11Jiahong Dong12Jiahong Dong13Jiahong Dong14Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, ChinaHepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaResearch Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, ChinaClinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, ChinaDepartment of General Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaClinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaHepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaHepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaHepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaResearch Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, ChinaClinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, ChinaHepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaResearch Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, ChinaHepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. More than 30% of patients with diagnosed HCC have abnormally high expression of fibroblast growth factor receptor 4 (FGFR4). Currently, clinical trials for a variety of FGFR4-specific inhibitors have started. However, the effect of these inhibitors is not ideal, and it is necessary to find a drug combination to synergistically exert anti-tumor effects. We found strong correlations between FGFR4 and HCC clinicopathological characteristics in the present study. After grouping patients according to FGFR4 expression, the key gene signatures were inputted the drug-gene related databases, which predicted several potential drug candidates. More importantly, to achieve the reliable and high throughput drug cytotoxicity assessment, we developed an efficient and reproducible agarose hydrogel microwells to generate uniform-sized multicellular tumor spheroids, which provide better mimicry of conventional solid tumors that can precisely represent anticancer drug candidates’ effects. Using high content screening, we quickly evaluated the enhanced anti-tumor effects of these combinations. Finally, we demonstrated that Parthenolide is a potential drug that can significantly enhance the clinical efficacy of FGFR4 receptor inhibitors. In general, we offered a new therapeutic way for FGFR4 positive HCC patients.https://www.frontiersin.org/articles/10.3389/fbioe.2022.1087656/fullhepatocellular carcinomaFGFR4 specific inhibitorsdrug combination3D cell cultureparthenolide |
| spellingShingle | Qi Wang Juan Liu Juan Liu Wenzhen Yin Dawei Sun Zhongsong Man Shangwei Jiang Xiufeng Ran Yuxin Su Yunfang Wang Yunfang Wang Yunfang Wang Jiahong Dong Jiahong Dong Jiahong Dong Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma Frontiers in Bioengineering and Biotechnology hepatocellular carcinoma FGFR4 specific inhibitors drug combination 3D cell culture parthenolide |
| title | Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma |
| title_full | Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma |
| title_fullStr | Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma |
| title_full_unstemmed | Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma |
| title_short | Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma |
| title_sort | generation of multicellular tumor spheroids with micro well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma |
| topic | hepatocellular carcinoma FGFR4 specific inhibitors drug combination 3D cell culture parthenolide |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.1087656/full |
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