Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE co...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522001022 |
| _version_ | 1811154393397985280 |
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| author | Senlin Li Siyu Chen Zhihui Dong Xingdong Song Xiuling Li Ziqi Huang Huiru Li Linzhuo Huang Ganyuan Zhuang Ran Lan Mingyan Guo Wende Li Phei Er Saw Lei Zhang |
| author_facet | Senlin Li Siyu Chen Zhihui Dong Xingdong Song Xiuling Li Ziqi Huang Huiru Li Linzhuo Huang Ganyuan Zhuang Ran Lan Mingyan Guo Wende Li Phei Er Saw Lei Zhang |
| author_sort | Senlin Li |
| collection | DOAJ |
| description | Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models. |
| first_indexed | 2024-04-10T04:14:49Z |
| format | Article |
| id | doaj.art-514a9fc4a0df4517b12807ff54c86af4 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-10T04:14:49Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-514a9fc4a0df4517b12807ff54c86af42023-03-12T04:20:59ZengElsevierActa Pharmaceutica Sinica B2211-38352023-03-01133967981Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancerSenlin Li0Siyu Chen1Zhihui Dong2Xingdong Song3Xiuling Li4Ziqi Huang5Huiru Li6Linzhuo Huang7Ganyuan Zhuang8Ran Lan9Mingyan Guo10Wende Li11Phei Er Saw12Lei Zhang13Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaGuangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou, 510663, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, ChinaDepartment of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, ChinaDepartment of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, ChinaDepartment of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, ChinaGuangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou, 510663, China; Corresponding authors. Tel./fax: +86 20 89205527, +86 20 84106800, +86 20 34070701.Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Corresponding authors. Tel./fax: +86 20 89205527, +86 20 84106800, +86 20 34070701.Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Corresponding authors. Tel./fax: +86 20 89205527, +86 20 84106800, +86 20 34070701.Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.http://www.sciencedirect.com/science/article/pii/S2211383522001022Hepatocellular carcinomaTubulin folding cofactor EChemoresistancesiRNA deliveryRNA interferenceNanoparticle |
| spellingShingle | Senlin Li Siyu Chen Zhihui Dong Xingdong Song Xiuling Li Ziqi Huang Huiru Li Linzhuo Huang Ganyuan Zhuang Ran Lan Mingyan Guo Wende Li Phei Er Saw Lei Zhang Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer Acta Pharmaceutica Sinica B Hepatocellular carcinoma Tubulin folding cofactor E Chemoresistance siRNA delivery RNA interference Nanoparticle |
| title | Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer |
| title_full | Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer |
| title_fullStr | Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer |
| title_full_unstemmed | Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer |
| title_short | Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer |
| title_sort | concurrent silencing of tbce and drug delivery to overcome platinum based resistance in liver cancer |
| topic | Hepatocellular carcinoma Tubulin folding cofactor E Chemoresistance siRNA delivery RNA interference Nanoparticle |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522001022 |
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