Treatment of human thyroid carcinoma cells with the g47delta oncolytic herpes simplex virus.
Treatment of human thyroid carcinoma cells with the g47delta oncolytic herpes simplex virus.
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DOI：
10.7314/apjcp.2015.16.3.1241
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发表时间：
2015-03
期刊：
影响因子：
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通讯作者：
Jia-ni Wang;Li-Hua Xu;W. Zeng;P. Hu;S. Rabkin;Renbin Liu
中科院分区：
文献类型：
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作者：
Jia-ni Wang;Li-Hua Xu;W. Zeng;P. Hu;S. Rabkin;Renbin Liu
背景甲状腺癌是最常见的内分泌系统恶性肿瘤。尽管大多数甲状腺癌患者的预后良好，但未分化甲状腺癌被认为是最具侵袭性的恶性肿瘤之一。目前的治疗方案不能提供显著的生存益处，迫切需要新的治疗方法。溶瘤性单纯疱疹病毒（oHSV）可能代表一种有前途的治疗癌症。在本研究中，我们研究了第三代HSV载体G47Δ对各种人甲状腺癌细胞系的体外治疗作用。两个皮下（s.c.）建立甲状腺未分化癌模型，评价G47Δ的体内抗肿瘤作用。材料与方法用G47Δ以不同的感染复数（MOI）感染人甲状腺癌细胞株ARO、FRO、WRO和KAT-5。每天计算感染细胞的存活率。两个皮下注射在Balb/c裸鼠中使用ARO和FRO细胞建立肿瘤模型，其瘤内（i. t.）用G47Δ或模拟物处理。记录肿瘤体积和小鼠存活时间。结果G47Δ对不同类型的甲状腺癌均有较强的细胞毒活性。对于ARO、FRO和KAT-5，在第5天，在MOI=0.01和MOI=0.1时，分别有超过30%和80%的细胞被杀死。WRO细胞对G47Δ表现出适度的敏感性，仅21%和38%的细胞被杀死。在南卡罗来纳州。G47Δ能显著抑制肿瘤生长，延长荷瘤小鼠的生存期。ARO和FRO肿瘤。结论oHSV G47Δ能有效杀伤不同类型的人甲状腺癌细胞。G47Δ在体内可显著抑制甲状腺未分化癌的生长，延长动物生存期。因此，G47Δ可能对甲状腺癌患者有很大的希望。
BACKGROUND Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, G47Δ, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of G47Δ. MATERIALS AND METHODS The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with G47Δat different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either G47Δor mock. Tumor volumes and mouse survival times were documented. RESULTS G47Δ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to G47Δ, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to G47Δ G47Δ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. CONCLUSIONS The oHSV G47Δ can effectively kill different types of human thyroid carcinomas in vitro. G47Δ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, G47Δ may hold great promise for thyroid cancer patients.