Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma

Autor: Rebecca Zhi Wen Ho, Eric Ming Hon Lee, Thi Bich Uyen Le, Aldo Prawira, Jun Hao Phua, Iris Jiu Hia Lim, Yusnita Binte Omar, Wendy Wan Li Chow, Thanh Chung Vu, Gee Keng Low, Hung Huynh, Kheng Wei Yeoh, Khee Chee Soo, Kok Ming Lee, Muhammad Zafrie Bin Saad, Mohamed Hakim Bin Mohd Nasir
Rok vydání: 2020
Předmět:
Zdroj: Cancers
Volume 12
Issue 4
Cancers, Vol 12, Iss 872, p 872 (2020)
ISSN: 2072-6694
DOI: 10.3390/cancers12040872
Popis: 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.
Databáze: OpenAIRE
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