Munkarah A, Chuang L, Lotzová E, Cook K, Morris M, Wharton J T
Department of Surgical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Gynecol Oncol. 1994 Nov;55(2):211-6. doi: 10.1006/gyno.1994.1279.
Taxotere, a semisynthetic derivative similar to taxol, has shown promising results in vitro and in preliminary in vivo studies. We have previously reported that taxol at 10 micrograms/ml suppressed the cytotoxic function and activation of natural killer cells and major histocompatibility nonrestricted (MHC-NR) T cells against the ovarian cell line OV-2774 and the erythroleukemia cell line K-562. In this paper, we investigated the effect of taxotere on lymphocyte function and found that a suppression of MHC-NR cytotoxicity of naive lymphocytes is only seen at higher doses of taxotere (50 micrograms/ml). At the concentrations of 10 and 50 micrograms/ml, taxotere did not have any effect on the cytotoxic function of IL-2-preactivated lymphocytes. On the contrary, both taxol and taxotere caused a significant suppression of lymphocyte growth and activation with IL-2 at 10 and 50 micrograms/ml. Both drugs (at the concentration of 10 micrograms/ml) were potent inhibitors of the growth of the tumor cell lines OV-2774 and K-562. In conclusion, despite the fact that taxotere shares with taxol a potent antitumor effect, it seems to be less suppressive for lymphocyte cytotoxicity, an effect clearly desirable in cancer therapy.
泰索帝是一种类似于紫杉醇的半合成衍生物,在体外和初步的体内研究中已显示出有前景的结果。我们之前报道过,10微克/毫升的紫杉醇可抑制自然杀伤细胞和主要组织相容性非限制性(MHC-NR)T细胞对卵巢癌细胞系OV-2774和红白血病细胞系K-562的细胞毒性功能及激活作用。在本文中,我们研究了泰索帝对淋巴细胞功能的影响,发现只有在较高剂量(50微克/毫升)的泰索帝作用下,才会观察到幼稚淋巴细胞的MHC-NR细胞毒性受到抑制。在10和50微克/毫升的浓度下,泰索帝对IL-2预激活淋巴细胞的细胞毒性功能没有任何影响。相反,10和50微克/毫升的紫杉醇和泰索帝都会显著抑制IL-2诱导的淋巴细胞生长和激活。两种药物(10微克/毫升浓度)都是肿瘤细胞系OV-2774和K-562生长的有效抑制剂。总之,尽管泰索帝与紫杉醇一样具有强大的抗肿瘤作用,但它对淋巴细胞细胞毒性的抑制作用似乎较小,这在癌症治疗中显然是一种理想的效果。