Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma
There is a need to improve the effectiveness of radiotherapy (RT) in hepatocellular carcinoma (HCC). Therefore, the purpose of this study was to explore the efficacy and toxicity of the anti-microtubule agent Vinorelbine as a radiosensitizer in HCC. The radio sensitivity of 16 HCC patient-derived xe...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/4/872 |
| _version_ | 1797571521576697856 |
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| author | Kheng Wei Yeoh Aldo Prawira Muhammad Zafrie Bin Saad Kok Ming Lee Eric Ming Hon Lee Gee Keng Low Mohamed Hakim Bin Mohd Nasir Jun Hao Phua Wendy Wan Li Chow Iris Jiu Hia Lim Yusnita Binte Omar Rebecca Zhi Wen Ho Thi Bich Uyen Le Thanh Chung Vu Khee Chee Soo Hung Huynh |
| author_facet | Kheng Wei Yeoh Aldo Prawira Muhammad Zafrie Bin Saad Kok Ming Lee Eric Ming Hon Lee Gee Keng Low Mohamed Hakim Bin Mohd Nasir Jun Hao Phua Wendy Wan Li Chow Iris Jiu Hia Lim Yusnita Binte Omar Rebecca Zhi Wen Ho Thi Bich Uyen Le Thanh Chung Vu Khee Chee Soo Hung Huynh |
| author_sort | Kheng Wei Yeoh |
| collection | DOAJ |
| description | There is a need to improve the effectiveness of radiotherapy (RT) in hepatocellular carcinoma (HCC). Therefore, the purpose of this study was to explore the efficacy and toxicity of the anti-microtubule agent Vinorelbine as a radiosensitizer in HCC. The radio sensitivity of 16 HCC patient-derived xenograft (PDX) models was determined by quantifying the survival fraction following irradiation in vitro, and Vinorelbine radio sensitization was determined by clonogenic assay. Ectopic HCC xenografts were treated with a single dose of 8 Gy irradiation and twice-weekly 3 mg/kg Vinorelbine. Tumor growth and changes in the proteins involved in DNA repair, angiogenesis, tumor cell proliferation, and survival were assessed, and the 3/16 (18.75%), 7/16 (43.75%), and 6/16 (37.5%) HCC lines were classified as sensitive, moderately sensitive, and resistant, respectively. The combination of RT and Vinorelbine significantly inhibited tumor growth, DNA repair proteins, angiogenesis, and cell proliferation, and promoted more apoptosis compared with RT or Vinorelbine treatment alone. Vinorelbine improved HCC tumor response to standard irradiation with no increase in toxicity. HCC is prevalent in less developed parts of the world and is mostly unresectable on presentation. Vinorelbine and conventional radiotherapy are cost-effective, well-established modalities of cancer treatment that are readily available. Therefore, this strategy can potentially address an unmet clinical need, warranting further investigation in early-phase clinical trials. |
| first_indexed | 2024-03-10T20:42:13Z |
| format | Article |
| id | doaj.art-a3396f722a5a42ad93e5a049683b7a3c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:42:13Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a3396f722a5a42ad93e5a049683b7a3c2023-11-19T20:37:35ZengMDPI AGCancers2072-66942020-04-0112487210.3390/cancers12040872Vinorelbine Augments Radiotherapy in Hepatocellular CarcinomaKheng Wei Yeoh0Aldo Prawira1Muhammad Zafrie Bin Saad2Kok Ming Lee3Eric Ming Hon Lee4Gee Keng Low5Mohamed Hakim Bin Mohd Nasir6Jun Hao Phua7Wendy Wan Li Chow8Iris Jiu Hia Lim9Yusnita Binte Omar10Rebecca Zhi Wen Ho11Thi Bich Uyen Le12Thanh Chung Vu13Khee Chee Soo14Hung Huynh15Department of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeLaboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore 169610, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeDepartment of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, SingaporeLaboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore 169610, SingaporeLaboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore 169610, SingaporeLaboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore 169610, SingaporeTan Chin Tuan Laboratory of Optical Imaging and Photodynamic & Proton Therapy, Division of Medical Sciences, National Cancer Centre, Singapore 169610, SingaporeLaboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore 169610, SingaporeThere is a need to improve the effectiveness of radiotherapy (RT) in hepatocellular carcinoma (HCC). Therefore, the purpose of this study was to explore the efficacy and toxicity of the anti-microtubule agent Vinorelbine as a radiosensitizer in HCC. The radio sensitivity of 16 HCC patient-derived xenograft (PDX) models was determined by quantifying the survival fraction following irradiation in vitro, and Vinorelbine radio sensitization was determined by clonogenic assay. Ectopic HCC xenografts were treated with a single dose of 8 Gy irradiation and twice-weekly 3 mg/kg Vinorelbine. Tumor growth and changes in the proteins involved in DNA repair, angiogenesis, tumor cell proliferation, and survival were assessed, and the 3/16 (18.75%), 7/16 (43.75%), and 6/16 (37.5%) HCC lines were classified as sensitive, moderately sensitive, and resistant, respectively. The combination of RT and Vinorelbine significantly inhibited tumor growth, DNA repair proteins, angiogenesis, and cell proliferation, and promoted more apoptosis compared with RT or Vinorelbine treatment alone. Vinorelbine improved HCC tumor response to standard irradiation with no increase in toxicity. HCC is prevalent in less developed parts of the world and is mostly unresectable on presentation. Vinorelbine and conventional radiotherapy are cost-effective, well-established modalities of cancer treatment that are readily available. Therefore, this strategy can potentially address an unmet clinical need, warranting further investigation in early-phase clinical trials.https://www.mdpi.com/2072-6694/12/4/872hepatocellular carcinomaradiotherapyradio sensitizationvinorelbineDNA repaircost-effectiveness |
| spellingShingle | Kheng Wei Yeoh Aldo Prawira Muhammad Zafrie Bin Saad Kok Ming Lee Eric Ming Hon Lee Gee Keng Low Mohamed Hakim Bin Mohd Nasir Jun Hao Phua Wendy Wan Li Chow Iris Jiu Hia Lim Yusnita Binte Omar Rebecca Zhi Wen Ho Thi Bich Uyen Le Thanh Chung Vu Khee Chee Soo Hung Huynh Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma Cancers hepatocellular carcinoma radiotherapy radio sensitization vinorelbine DNA repair cost-effectiveness |
| title | Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma |
| title_full | Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma |
| title_fullStr | Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma |
| title_full_unstemmed | Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma |
| title_short | Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma |
| title_sort | vinorelbine augments radiotherapy in hepatocellular carcinoma |
| topic | hepatocellular carcinoma radiotherapy radio sensitization vinorelbine DNA repair cost-effectiveness |
| url | https://www.mdpi.com/2072-6694/12/4/872 |
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