Differentiation ability of a Cell Line of Human Cervical Argyrophil Small Cell Carcinoma (ASCC) and Development of Effective Treatment of ASCC

1)分化诱导剂对宫颈鳞癌细胞系特性的影响为探讨宫颈嗜银小细胞癌(ASCC)的起源，我们研究了已知的分化诱导剂二丁酰环腺苷(Db-cAMP)对ASCC细胞系TC-Y1K特性的影响，这是一种有用的ASCC体外实验模型。经dB-cAMP处理后的TC-YIK细胞，检测到巨噬细胞特异性抗原标志物CD14和HLADR及干扰素-γ基因和蛋白的表达：大部分细胞α-丁酸萘酯酶染色阳性，部分细胞对溶血微球菌有吞噬和吸附作用。GM-CSF还能促进TC-YIK细胞的增殖。这些结果表明，dB-cAMP促进了ASCC细胞向巨噬细胞系的分化。相反，部分细胞呈现星状形态改变，提示经dB-cAMP处理后有神经元分化。2)顺铂诱导TC-YIK细胞凋亡及干扰素-γ对顺铂诱导TC-YIK细胞凋亡的影响为探讨干扰素-γ能否作为治疗癌药物顺铂的辅助药物，探讨干扰素-γ对顺铂诱导TC-YIK细胞凋亡的作用及机制。经干扰素-γ处理后，顺铂对TC-YIK细胞的凋亡诱导作用增强。TC-YIK细胞Fas抗原的表达程度与细胞凋亡率的增加程度呈平行关系。Caspase抑制剂Z-VADfmk可完全抑制干扰素-γ对顺铂诱导的细胞凋亡的促进作用。提示干扰素-γ可通过上调TC-YIK细胞表面Fas抗原的表达来增强顺铂诱导的细胞凋亡，干扰素-γ可作为治疗癌的辅助药物。

1)Effect of a differentiation inducer on characteristics of an ASCC cell line To investigate the origin of argyrophil small cell carcinoma (ASCC of the uterine cervix, we examined the influence of dibutyryl cyclic AMP (dB-cAMP), a known differentiation inducer, on characteristics of an ASCC cell line, TC-YIK, which has been demonstrated to be a useful in vitro experimental model of ASCC. In TC-YIK cells after treatment with dB-cAMP, specific antigenic markers of macrophage (CD14 and HLA-DR), and IFN-γ mRNA and protein were detected: Most of the cells were positive for α-naphtyl buyrate esterase stain, and some of the cells showed phagocytosis and adsorption of Micrococcus lysodeikticus. Furthermore, GM-CSF accelerated the proliferation of TC-YIK cells. These results indicate that dB-cAMP promotes a differentiation process to macrophage lineage in the ASCC cell line. In contrast, some of the cells showed stellate morphological changes, suggesting a neuronal differentiation after treatment with dB-cAMP. Thus, TC-YIK has been shown to differentiate both into macrophage lineage and neuronal cells, suggesting that ASCC may originate from undifferentiated stem cells.2) Induction of apoptosis in TC-YIK cells by CDDP and effect of IFN-γ on the CDDP-induced apoptosis To investigate if IFN-γ can be used as an auxiliary drug of CDDP, a therapeutic drug for ASCC, we examined the effect and mechanism of IFN-γ on CDDP-induced apoptosis of TC-YIK. Apoptosis induction in TC-YIK cells by CDDP was increased after treatment with IFN-γ. The extent of Fas antigen expression on TC-YIK cells was in parallel with that of increase in the apoptosis of the cells. The increase of CDDP-induced apoptosis by IFN-γ was completely inhibited by a caspase inhibitor, Z-VADfmk. These results suggest that IFN-γ increases the CDDP-induced apoptosis through the increase in Fas antigen expression on TC-YIK cells, and that INF-γ could be used as an auxiliary therapeutic drug for ASCC.