Sacks P G, Oke V, Calkins D P, Vasey T, Terry N H
Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Cell Physiol. 1990 Aug;144(2):237-43. doi: 10.1002/jcp.1041440209.
The growth of multicellular tumor spheroids, MTSs, from squamous carcinoma line MDA 886Ln was inhibited by beta-all-trans retinoic acid (RA). Inhibition occurred within 3 to 5 days of treatment, and MTS size then remained static for up to 2 weeks. Although their growth stopped, 10-day-treated MTSs incorporated [3H]thymidine into trichloroacetic acid-precipitable material, and the [3H]thymidine labeling index, determined by autoradiography, was equivalent between control and RA-treated MTSs. Bivariate flow cytometric analysis of bromodeoxyuridine-labeled MTSs showed equivalent S phase progression of labeled cells over an 8-hour chase. MTS growth stasis was not related to RA-induced cell cycle effects. Monitoring of MTSs for cell sloughing showed no significant cell shedding that could account for stasis. Quantitation of cell number and DNA content per MTS showed an RA-induced decrease. This was confirmed by histological analysis, which demonstrated the temporal appearance of acellular areas. MTS growth statis is thus related to an RA-induced cell loss in this MTS model for squamous carcinomas.
β-全反式维甲酸（RA）抑制了源自鳞状细胞癌系MDA 886Ln的多细胞肿瘤球体（MTSs）的生长。在治疗的3至5天内出现抑制作用，随后MTS大小在长达2周的时间内保持稳定。尽管它们的生长停止了，但经10天治疗的MTSs仍将[3H]胸腺嘧啶核苷掺入三氯乙酸可沉淀物质中，并且通过放射自显影测定的[3H]胸腺嘧啶核苷标记指数在对照和经RA处理的MTSs之间相当。对溴脱氧尿苷标记的MTSs进行双变量流式细胞术分析显示，在8小时的追踪过程中，标记细胞的S期进展相当。MTS生长停滞与RA诱导的细胞周期效应无关。对MTSs进行细胞脱落监测显示，没有明显的细胞脱落可解释停滞现象。对每个MTS的细胞数量和DNA含量进行定量显示RA诱导了减少。组织学分析证实了这一点，其显示了无细胞区域的暂时出现。因此，在这个鳞状细胞癌的MTS模型中，MTS生长停滞与RA诱导的细胞丢失有关。
