Kaiho T, Sekiya S, Inaba N, Shirotake S, Katoh T, Kobayashi O, Ishige H, Takamizawa H
Nihon Sanka Fujinka Gakkai Zasshi. 1983 Jan;35(1):1-9.
Both the sensitivity to MTX and hCG secretion were compared in two choriocarcinoma cell lines (BeWo and HCCM-5) and study on mechanisms about MTX-resistance was described. The uptake of nucleotides and protein precursors was decreased in dose-dependent manner in both cell lines when exposed to MTX, but HCCM-5 cells showed more sensitivity to MTX. In HCCM-5 cells, both hCG and hCG-beta levels in the medium were decreased with exposure to 10(-9)M MTX, but they tended to increase when exposed to higher concentration of MTX in contrast to the inhibition of 3H-thymidine uptake. However, in BeWo cells, an inverse relationship between the incorporation of 3H-thymidine and secretion of hCG was not clearly observed. The content of dihydrofolate reductase (DHFR) in HCCM-5 cells was about one-half of that in BeWo cells. Although the peak of 3H-MTX incorporation was observed at 120 minutes in both cell lines, HCCM-5 cells incorporated about 4 times higher 3H-MTX than BeWo cells. The difference of sensitivity to MTX between those two cell lines seems to be concerned with both the decrease of MTX transport and increase of intracellular DHFR levels.
在两种绒毛膜癌细胞系(BeWo和HCCM-5)中比较了对甲氨蝶呤(MTX)的敏感性和人绒毛膜促性腺激素(hCG)分泌,并描述了关于MTX耐药机制的研究。当暴露于MTX时,两种细胞系中核苷酸和蛋白质前体的摄取均呈剂量依赖性降低,但HCCM-5细胞对MTX表现出更高的敏感性。在HCCM-5细胞中,暴露于10(-9)M MTX时,培养基中的hCG和hCG-β水平均降低,但与3H-胸腺嘧啶摄取的抑制相反,当暴露于更高浓度的MTX时,它们趋于增加。然而,在BeWo细胞中,未清楚观察到3H-胸腺嘧啶掺入与hCG分泌之间的反向关系。HCCM-5细胞中二氢叶酸还原酶(DHFR)的含量约为BeWo细胞中的一半。尽管在两种细胞系中均在120分钟时观察到3H-MTX掺入的峰值,但HCCM-5细胞掺入的3H-MTX比BeWo细胞高约4倍。这两种细胞系对MTX敏感性的差异似乎与MTX转运的减少和细胞内DHFR水平的增加有关。