Sagawa T, Yamashita K, Kawamura M, Shimizu T
Nihon Sanka Fujinka Gakkai Zasshi. 1986 Feb;38(2):203-9.
Cis-platinum (CDDP) was investigated in vitro and in vivo for its ability to inhibit the growth of Methotrexate (MTX)-resistant choriocarcinoma cell line (BeWo) and was compared with the effect of MTX and Actinomycin D (ACD). Each drug was added into medium (RPMI 1640 containing 10% FBS) for 1 hr. at the concentration of peak plasma level in clinical use (CDDP 7 X 10(-6)M, MTX 10(-6)M, and ACD 8 X 10(-8)M), or for 48 hrs. at one-tenth of the level. CDDP inhibited the cell growth to 40% of control at 7 X 10(-6)M for 1 hr., and 25% at 7 X 10(-7) M for 48 hrs. And ACD suppressed the cell growth to 10% at both 8 X 10(-8)M for 1 hr. and 8 X 10(-9)M for 48 hrs. But MTX did not inhibit the cell growth at 10(-6)M for 1 hr., and inhibited to 60% of control at 10(-7)M for 48 hrs. On the other hand, BeWo transplanted to athymic nude mice (CD-1(ICR) nu/nu) was treated with intraperitoneal injections of CDDP (1.4 mg/kg/day for 4 consecutive days in a week and repeated for 2 and 4 weeks), MTX (2mg/kg/day for 4 consecutive days in a week and repeated for 2 weeks), and ACD (90 micrograms/kg/day for 4 consecutive days in a week and repeated for 2 and 4 weeks). The suppression of the tumor growth was seen in CDDP-treated group (TRW/CRW = 6.5%) and ACD-treated group (TRW/CRW = 29%) after 2 courses of treatment, but no apparent suppression was shown in the MTX-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
对顺铂(CDDP)进行了体外和体内研究,以考察其抑制甲氨蝶呤(MTX)耐药性绒癌细胞系(BeWo)生长的能力,并与MTX和放线菌素D(ACD)的作用进行比较。每种药物以临床使用时的血浆峰值浓度(CDDP 7×10⁻⁶M、MTX 10⁻⁶M和ACD 8×10⁻⁸M)加入培养基(含10%胎牛血清的RPMI 1640)中1小时,或以该浓度的十分之一加入48小时。CDDP在7×10⁻⁶M浓度下作用1小时,可将细胞生长抑制至对照的40%,在7×10⁻⁷M浓度下作用48小时,抑制至25%。ACD在8×10⁻⁸M浓度下作用1小时以及在8×10⁻⁹M浓度下作用48小时,均将细胞生长抑制至10%。但MTX在10⁻⁶M浓度下作用1小时未抑制细胞生长,在10⁻⁷M浓度下作用48小时抑制至对照的60%。另一方面,将BeWo移植到无胸腺裸鼠(CD-1(ICR) nu/nu)体内,分别腹腔注射CDDP(每周连续4天,每天1.4mg/kg,重复2周和4周)、MTX(每周连续4天,每天2mg/kg,重复2周)和ACD(每周连续4天,每天90μg/kg,重复2周和4周)。治疗2个疗程后,CDDP治疗组(TRW/CRW = 6.5%)和ACD治疗组(TRW/CRW = 29%)出现肿瘤生长抑制,但MTX治疗组未表现出明显抑制。(摘要截选至250字)