Martinsson P, Nygren P, Fridborg H, Nilsson K, Kristensen J, Larsson R
Department of Clinical Pharmacology, University Hospital, Uppsala University, Sweden.
Eur J Clin Pharmacol. 1997;52(3):199-203. doi: 10.1007/s002280050274.
The fluorometric microculture cytotoxic assay was employed for characterisation of the cytotoxic effect of cyclosporin A (CsA) and its non-immunosuppressive analogue SDZ PSC 833, [3-keto-Bmt1]-[Val2]-cyclosporin (PSC) in tumour cells from patients with haematological or solid tumours.
Tumour cells from patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin's lymphoma (NHL) were found to be more sensitive to both drugs than those of tumour cells from patients with acute lymphocytic leukemia (ALL), acute myoblastic leukaemia (AML) and various solid tumours. There was a close correlation between the effects of the two drugs (correlation coefficient 0.71), but CsA was slightly more active than PSC in most diagnoses. No tumour cells sample showed sensitivity to PSC without also being sensitive to CsA. There was a moderate level of correlation between the activity pattern of CsA and doxorubicin (correlation coefficient 0.66), whereas the correlations with other cytostatics, such as vincristine, cytarabine and melphalan, were low (correlation coefficient -0.11 to 0.33).
The results indicate that PSC shares the direct cytotoxic properties of CsA, but is slightly less potent. Clinical testing of the cytotoxic effect of these agents in haematological malignancies seems warranted and the apparent non-cross-resistance with standard agents makes cyclosporins a potentially useful adjunct to chemotherapy in those diagnoses.
采用荧光微量培养细胞毒性试验来表征环孢素A（CsA）及其非免疫抑制类似物SDZ PSC 833，即[3-酮基-Bmt1]-[Val2]-环孢素（PSC）对血液系统或实体瘤患者肿瘤细胞的细胞毒性作用。
发现慢性淋巴细胞白血病（CLL）或非霍奇金淋巴瘤（NHL）患者的肿瘤细胞比急性淋巴细胞白血病（ALL）、急性粒细胞白血病（AML）和各种实体瘤患者的肿瘤细胞对这两种药物更敏感。两种药物的作用之间存在密切相关性（相关系数为0.71），但在大多数诊断中，CsA的活性略高于PSC。没有肿瘤细胞样本显示对PSC敏感而对CsA不敏感。CsA与阿霉素的活性模式之间存在中等程度的相关性（相关系数为0.66），而与其他细胞抑制剂，如长春新碱、阿糖胞苷和美法仑的相关性较低（相关系数为-0.11至0.33）。
结果表明，PSC具有与CsA相同的直接细胞毒性特性，但效力略低。在血液系统恶性肿瘤中对这些药物的细胞毒性作用进行临床试验似乎是有必要的，并且与标准药物明显的非交叉耐药性使得环孢素在那些诊断中成为化疗的潜在有用辅助药物。
