Yeoh Kheng Wei, Prawira Aldo, Saad Muhammad Zafrie Bin, Lee Kok Ming, Lee Eric Ming Hon, Low Gee Keng, Mohd Nasir Mohamed Hakim Bin, Phua Jun Hao, Chow Wendy Wan Li, Lim Iris Jiu Hia, Omar Yusnita Binte, Ho Rebecca Zhi Wen, Le Thi Bich Uyen, Vu Thanh Chung, Soo Khee Chee, Huynh Hung
Department of Radiation Oncology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore 169610, Singapore.
Cancers (Basel). 2020 Apr 3;12(4):872. doi: 10.3390/cancers12040872.
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.
有必要提高肝细胞癌（HCC）放射治疗（RT）的有效性。因此，本研究的目的是探讨抗微管药物长春瑞滨作为HCC放射增敏剂的疗效和毒性。通过体外照射后定量存活分数来确定16个HCC患者来源的异种移植（PDX）模型的放射敏感性，并通过克隆形成试验确定长春瑞滨的放射增敏作用。将异位HCC异种移植瘤用单次8 Gy照射和每周两次3 mg/kg长春瑞滨进行治疗。评估肿瘤生长以及参与DNA修复、血管生成、肿瘤细胞增殖和存活的蛋白质的变化，16个HCC细胞系中分别有3/16（18.75%）、7/16（43.75%）和6/16（37.5%）被分类为敏感、中度敏感和耐药。与单独的RT或长春瑞滨治疗相比，RT与长春瑞滨联合使用显著抑制肿瘤生长、DNA修复蛋白、血管生成和细胞增殖，并促进更多细胞凋亡。长春瑞滨提高了HCC肿瘤对标准照射的反应，且未增加毒性。HCC在世界较不发达地区普遍存在，大多数患者就诊时无法切除。长春瑞滨和传统放疗是具有成本效益、成熟且容易获得的癌症治疗方式。因此，该策略可能满足未被满足的临床需求，值得在早期临床试验中进一步研究。
