氯化甲基汞对小细胞肺癌NCI-H446细胞的增殖抑制作用

Inhibitory effect of methylmercury on proliferation of human small cell lung cancer cells

目的:探讨氯化甲基汞(MMC)对人小细胞肺癌NCI-H446细胞的增殖抑制作用,为MMC治疗小细胞肺癌提供实验依据。方法:采用MTT比色法,分别测定不同浓度的MMC、顺铂(DDP)、As2O3作用于NCI-H446细胞后的吸光度A570值,计算增殖抑制率;并应用皮下注射法建立裸鼠NCI-H446移植瘤模型,灌胃法给予模型鼠MMC或生理盐水,停药后测量肿物长短径,HE染色观察瘤体细胞形态学改变。结果:MMC各浓度组A570值均低于对照组,自2.5μmol/L起各浓度组之间A570值均存在显著性差异(P<0.05),且同一浓度各时间之间均存在显著性差异(P<0.05);DDP、As2O3各浓度组A570值亦均低于对照组,其中DDP与MMC两者之间比较无统计学差异,在作用24、48、72小时的每一个浓度组,MMC和DDP的增殖抑制率均大于As2O3。给予MMC灌胃的荷瘤鼠肿瘤体积小于对照组,差异有显著性(P<0.05),HE染色见坏死细胞增多。结论:MMC对人小细胞肺癌NCI-H446细胞有增殖抑制作用,并存在着时间和剂量效应关系,其增殖抑制作用与顺铂相当,强于As2O3。

Objective： To investigate the inhibition of methylmercury on proliferation of human small cell lung cancer NCI-H446 and to compare with As2O3 and cisp latin.Methods： MTT chromatometry was adopted. Cultured NCI-H446 cells were incubated with different doses of methylmercury, As2O3, or cisplatin at 2.5,5,10,20,40/maol/L. The optical density 0D570 value were detected to calculate the inhibitory rate of preliferation. The nude mice model beating tumor was constructed by subcutaneous injection with transplanting NCI-H446 cells. MMC was used at 10 mg/kg in administration with normal saline as the control.Tumor size was measured and tumor volume was calculated.Then the morphologic change was observed by HE stainning. Results： OD570 value of methylmercury groups were lower than that of the control groups at any doses and the difference was significant from 2.5 μmol/L group（ P 〈 0.05）. The difference of the OD570 value of methylmereury groups trader the same concentration among the different times were significant （ P 〈 0.05）; 0D570 value of As2O3 and cisplatin groups were also lower than that of the control groups. There was no significant difference with MMC and cisplatin. 0D570 value of MMC and DDP groups were higher than that of As2O3 groups. The volume of the tumor of the experiment groups was smaller than that of normal saline group, and the necrocytosis was more than that of normal saline group by HE stainning. Condusion： Methylmercury could inhibit the proliferation of human small cell lung cancer NCI-H446,and the effect is both time- and dose-dependence. At the same doses,this effect may be equal to cisplatin＇s and stronger than As2O3＇s.