Inhibitory effects of 22-oxa-calcitriol and all-trans retinoic acid on the growth of a canine osteosarcoma derived cell-line in vivo and its pulmonary metastasis in vivo
Inhibitory effects of 22-oxa-calcitriol and all-trans retinoic acid on the growth of a canine osteosarcoma derived cell-line in vivo and its pulmonary metastasis in vivo
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DOI：
10.1053/rvsc.1999.0360
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发表时间：
2000-02-01
影响因子：
2.4
通讯作者：
Fujinaga, T
中科院分区：
文献类型：
--
作者：
Barroga, EF;Kadosawa, T;Fujinaga, T
肺转移是犬骨肉瘤死亡的主要原因，也是成功治疗的主要障碍。然而，肿瘤分化的剩余能力及其对细胞凋亡的易感性可能被用来抑制其生长和转移特性。以高转移性骨肉瘤（HMPOS）细胞株为实验材料，研究22-氧-骨化三醇（OCT）和全反式维甲酸（ATRA）对裸鼠皮下骨肉瘤生长和肺转移的抑制作用。体外处理，细胞形态拉长，碱性磷酸酶活性和染色增加。体内肿瘤生长明显受到抑制，OCT和ATRA联合治疗（OCT + ATRA）在1.0 μ g kg（-1）体重的浓度下，每周皮下给药3次，连续5周，具有更强的协同抑制作用。对照组小鼠的皮下细胞由成骨细胞样细胞和分离的成软骨细胞样细胞组成，但在所有治疗小鼠中形成了几个类骨区域和胶原组织的数量增加。定点大转移结节仅在所有对照小鼠中发生。在接受ATRA治疗的6只小鼠中，只有2只发生了微转移结节。但结节大小、数量、肺湿重均显著减少。在OCT或OCT + ATRA治疗的小鼠中未见转移。本研究表明，这些药物皮下治疗可诱导生长和肺转移的抑制，并提示其分化和诱导凋亡活性可能是抗肿瘤作用的原因。这些药物可能是有用的，在临床辅助治疗犬骨肉瘤。(C) 2000 Harcourt出版社有限公司
Pulmonary metastasis is a major cause of death and a major obstacle to the successful treatment of canine osteosarcoma. However, the residual capacity of the neoplasia for differentiation and its susceptibility to undergo apoptosis may be used to suppress its growth and metastatic properties. The highly metastasizing POS (HMPOS) canine osteosarcoma cell line which preferentially metastasize to the lungs was used to test the possible efficacy of 22-oxa-calcitriol (OCT) and all-trans retinoic acid (ATRA) to inhibit growth and pulmonary metastasis of the subcutaneously grown osteosarcoma in nude mice. Treatments in vitro, morphologically elongated and increased alkaline phosphatase activity and staining of cells. Tumour growth in vivo was inhibited significantly and the combination treatment of OCT and ATRA (OCT + ATRA) exerted a synergistic and stronger suppression at concentration of 1.0 mu g kg(-1) body weight when given subcutaneously three times a week for 5 weeks. The subcutaneous rumours of the control mice consisted of osteoblast-like cells and isolated chondroblast-like cells, but formed several areas of osteoid and increased amount of collagen tissue in all treated mice. Pinpoint macrometastatic nodules developed only in all control mice. Micrometastatic nodule developed only in two of six mice treated with ATRA. However, nodule size and number, and lung wet weight were all reduced significantly. Metastasis were not seen in the mice treated with OCT or OCT + ATRA. This study demonstrated that inhibition of growth and pulmonary metastasis was induced by subcutaneous treatment with these drugs and suggest that both its differentiating and apoptotic inducing activities may be responsible for the antitumour effects. These drugs may be useful in the clinic as an adjunct for the treatment of canine osteosarcoma. (C) 2000 Harcourt Publishers Ltd.