Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma
Abstract Background Ras activation is a frequent event in hepatocellular carcinoma (HCC). Combining a RAS inhibitor with traditional clinical therapeutics might be hampered by a variety of side effects, thus hindering further clinical translation. Herein, we report on integrating an IR820 nanocapsul...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-00923-3 |
| _version_ | 1811212848083238912 |
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| author | Bolin Wu Yanchi Yuan Jiayin Liu Haitao Shang Jing Dong Xitian Liang Dongxu Wang Yichi Chen Chunyue Wang Yang Zhou Hui Jing Wen Cheng |
| author_facet | Bolin Wu Yanchi Yuan Jiayin Liu Haitao Shang Jing Dong Xitian Liang Dongxu Wang Yichi Chen Chunyue Wang Yang Zhou Hui Jing Wen Cheng |
| author_sort | Bolin Wu |
| collection | DOAJ |
| description | Abstract Background Ras activation is a frequent event in hepatocellular carcinoma (HCC). Combining a RAS inhibitor with traditional clinical therapeutics might be hampered by a variety of side effects, thus hindering further clinical translation. Herein, we report on integrating an IR820 nanocapsule-augmented sonodynamic therapy (SDT) with the RAS inhibitor farnesyl-thiosalicylic acid (FTS). Using cellular and tumor models, we demonstrate that combined nanocapsule-augmented SDT with FTS induces an anti-tumor effect, which not only inhibits tumor progression, and enables fluorescence imaging. To dissect the mechanism of a combined tumoricidal therapeutic strategy, we investigated the scRNA-seq transcriptional profiles of an HCC xenograft following treatment. Results Integrative single-cell analysis identified several clusters that defined many corresponding differentially expressed genes, which provided a global view of cellular heterogeneity in HCC after combined SDT/FTS treatment. We conclude that the combination treatment suppressed HCC, and did so by inhibiting endothelial cells and a modulated immunity. Moreover, hepatic stellate secretes hepatocyte growth factor, which plays a key role in treating SDT combined FTS. By contrast, enrichment analysis estimated the functional roles of differentially expressed genes. The Gene Ontology terms “cadherin binding” and “cell adhesion molecule binding” and KEGG pathway “pathway in cancer” were significantly enriched by differentially expressed genes after combined SDT/FTS therapy. Conclusions Thus, some undefined mechanisms were revealed by scRNA-seq analysis. This report provides a novel proof-of-concept for combinatorial HCC-targeted therapeutics that is based on a non-invasive anti-tumor therapeutic strategy and a RAS inhibitor. |
| first_indexed | 2024-04-12T05:36:11Z |
| format | Article |
| id | doaj.art-f5bf4e69bdc743a786e0c460782ae5e4 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-12T05:36:11Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-f5bf4e69bdc743a786e0c460782ae5e42022-12-22T03:45:51ZengBMCJournal of Nanobiotechnology1477-31552021-06-0119111510.1186/s12951-021-00923-3Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinomaBolin Wu0Yanchi Yuan1Jiayin Liu2Haitao Shang3Jing Dong4Xitian Liang5Dongxu Wang6Yichi Chen7Chunyue Wang8Yang Zhou9Hui Jing10Wen Cheng11Department of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Radiation Oncology, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Radiology, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Harbin Medical University Cancer HospitalAbstract Background Ras activation is a frequent event in hepatocellular carcinoma (HCC). Combining a RAS inhibitor with traditional clinical therapeutics might be hampered by a variety of side effects, thus hindering further clinical translation. Herein, we report on integrating an IR820 nanocapsule-augmented sonodynamic therapy (SDT) with the RAS inhibitor farnesyl-thiosalicylic acid (FTS). Using cellular and tumor models, we demonstrate that combined nanocapsule-augmented SDT with FTS induces an anti-tumor effect, which not only inhibits tumor progression, and enables fluorescence imaging. To dissect the mechanism of a combined tumoricidal therapeutic strategy, we investigated the scRNA-seq transcriptional profiles of an HCC xenograft following treatment. Results Integrative single-cell analysis identified several clusters that defined many corresponding differentially expressed genes, which provided a global view of cellular heterogeneity in HCC after combined SDT/FTS treatment. We conclude that the combination treatment suppressed HCC, and did so by inhibiting endothelial cells and a modulated immunity. Moreover, hepatic stellate secretes hepatocyte growth factor, which plays a key role in treating SDT combined FTS. By contrast, enrichment analysis estimated the functional roles of differentially expressed genes. The Gene Ontology terms “cadherin binding” and “cell adhesion molecule binding” and KEGG pathway “pathway in cancer” were significantly enriched by differentially expressed genes after combined SDT/FTS therapy. Conclusions Thus, some undefined mechanisms were revealed by scRNA-seq analysis. This report provides a novel proof-of-concept for combinatorial HCC-targeted therapeutics that is based on a non-invasive anti-tumor therapeutic strategy and a RAS inhibitor.https://doi.org/10.1186/s12951-021-00923-3Hepatocellular carcinomaSonodynamic therapyscRNA-seqRAS inhibitor |
| spellingShingle | Bolin Wu Yanchi Yuan Jiayin Liu Haitao Shang Jing Dong Xitian Liang Dongxu Wang Yichi Chen Chunyue Wang Yang Zhou Hui Jing Wen Cheng Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma Journal of Nanobiotechnology Hepatocellular carcinoma Sonodynamic therapy scRNA-seq RAS inhibitor |
| title | Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma |
| title_full | Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma |
| title_fullStr | Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma |
| title_full_unstemmed | Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma |
| title_short | Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma |
| title_sort | single cell rna sequencing reveals the mechanism of sonodynamic therapy combined with a ras inhibitor in the setting of hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Sonodynamic therapy scRNA-seq RAS inhibitor |
| url | https://doi.org/10.1186/s12951-021-00923-3 |
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