Radiobiological Characterization of Canine Malignant Melanoma Cell Lines with Different Types of Ionizing Radiation and Efficacy Evaluation with Cytotoxic Agents
Radiobiological Characterization of Canine Malignant Melanoma Cell Lines with Different Types of Ionizing Radiation and Efficacy Evaluation with Cytotoxic Agents
复制标题
DOI：
10.3390/ijms20040841
复制
发表时间：
2019-02-02
影响因子：
5.6
通讯作者：
Kato, Takamitsu A.
中科院分区：
文献类型：
--
作者：
Yoshikawa, Hiroto;Sunada, Shigeaki;Kato, Takamitsu A.
犬恶性黑色素瘤（CMM）是一种局部和全身侵袭性癌症，与人类粘膜黑色素瘤具有许多生物学和临床特征。大分割放射治疗方案已用于治疗 CMM，但对其放射生物学知之甚少。该试点研究旨在研究 CMM 细胞系对各种电离辐射和细胞毒性药物的反应，以更好地了解这种犬类癌症。通过有氧和缺氧条件下的克隆存活测定评估四种 CMM 细胞系，并计算 Cs-137、6 兆伏 (MV) 光子或碳离子照射后的参数，如 αβ (/) 比率、氧增强比 (OER) 和相对生物有效性 (RBE)。还评估了六种细胞毒性药物（顺铂、喜树碱、丝裂霉素 C、博来霉素、甲磺酸甲酯和依托泊苷）的功效。在 6 MV 光子的有氧条件下，四种细胞系的 / 比率范围为 0.3 至 >100，表明细胞敏感性存在很大差异。与有氧条件相比，该比率在缺氧条件下增加，并且在 Cs-137 和 6 MV 光子处理中更为显着。 4 个细胞系中有 3 个在 D-10 时碳的 OER 低于 Cs-137。 RBE值一般随着LET的增加而增加。不同的细胞系对不同的细胞毒剂表现出敏感性/耐药性。这项研究表明，CMM 具有广泛的放射敏感性，缺氧可以降低放射敏感性，这表明广泛使用的大分割方案可能并不适合所有 CMM 患者。几种从未经过临床评估的细胞毒性药物可以改善治疗结果。
Canine malignant melanoma (CMM) is a locally and systemically aggressive cancer that shares many biological and clinical characteristics with human mucosal melanoma. Hypofractionated radiation protocols have been used to treat CMM but little is known about its radiation biology. This pilot study is designed to investigate response of CMM cell lines to various ionizing radiations and cytotoxic agents to better understand this canine cancer. Four CMM cell lines were evaluated by clonogenic survival assay under aerobic and hypoxic conditions and parameters such as alpha beta (/) ratio, oxygen enhancement ratio (OER), and relative biological effectiveness (RBE) were calculated after Cs-137, 6 megavoltage (MV) photon, or carbon ion irradiation. Six cytotoxic agents (cisplatin, camptothecin, mitomycin C, bleomycin, methtyl methanesulfonate and etoposide) were also assessed for their efficacy. Under aerobic condition with 6 MV photon, the / ratio of the four cell lines ranged from 0.3 to >100, indicating a wide variation of cellular sensitivity. The ratio increased under hypoxic condition compared to aerobic condition and this was more dramatic in Cs-137 and 6 MV photon treatments. OER of carbon was lower than Cs-137 at D-10 in 3 of the 4 cell lines. The RBE values generally increased with the increase of LET. Different cell lines showed sensitivity/resistance to different cytotoxic agents. This study revealed that CMM has a wide range of radiosensitivity and that hypoxia can reduce it, indicating that widely used hypofractionated protocols may not be optimal for all CMM patients. Several cytotoxic agents that have never been clinically assessed can improve treatment outcome.