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目的:研究米非司酮(MIF)裸鼠体内逆转人宫颈癌Hela/MMC细胞系对丝裂霉素(MMC)耐药的效果及其作用机制。方法:以人宫颈癌Hela细胞耐药亚系(Hela/MMC细胞)为材料,建立裸鼠移植瘤模型,随机分为4组:空白对照组、单用MIF组、单用MMC组、联合用药组,观察用药后移植瘤的体积、瘤重及裸鼠体重,光镜下观察瘤组织病理学改变及裸鼠主要脏器的病理情况,免疫组织化学染色法检测移植瘤增殖细胞相关核抗原ki-67的表达。结果:联合用药组平均瘤体积(288.61±93.70)mm3较对照组(998.93±219.10)mm3及单用MIF组(903.01±288.51)mm3显著降低(P<0.01),较MMC组(693.33±230.75)mm3明显降低(P<0.05);联合用药组平均瘤重(0.14±0.04)g较对照组(0.41±0.07)g、单用MIF组(0.37±0.10)g及单用MMC组(0.32±0.08)g明显降低,差异有显著性(P<0.01);联用组ki-67表达的平均光密度值(OD)(0.21±0.01)较对照组(0.56±0.04)、单用MIF组(0.37±0.02)及单用MMC组(0.55±0.04)明显降低,差异有显著性(P<0.01);单用MIF组平均光密度值较对照组及单用MMC组显著降低(P<0.01),对照组与单用MMC组比较,差异无显著性(P>0.05)。联合用药组肿瘤形态出现明显坏死,各组裸鼠体重无显著性差异(P>0.05),裸鼠主要脏器无明显病理变化。结论:米非司酮裸鼠体内可逆转Hela/MMC细胞对MMC的耐药性且无明显毒副作用,其逆转耐药机制可能与降低增殖细胞相关核抗原(ki-67)的表达有关。
Objective: To investigate the effect and mechanism of reversing the drug resistance of mitomycin C (MMC) in human cervical cancer Hela / MMC cell line in MIF nude mice. Methods: Hela / MMC cells were used to establish the nude mice xenografts model and divided randomly into 4 groups: blank control group, single MIF group, single MMC group, combination therapy The tumor volume, tumor weight and body weight of nude mice were observed after treatment. The pathological changes of tumor tissues and the pathological changes of major organs in nude mice were observed under light microscope. Immunohistochemical staining was used to detect the expression of proliferating cell nuclear antigen ki -67 expression. Results: The mean tumor volume in the combination group (288.61 ± 93.70) mm3 was significantly lower than that in the control group (998.93 ± 219.10 mm3) and the MIF group (903.01 ± 288.51) mm3 (693.33 ± 230.75) (0.41 ± 0.07) g in the combined treatment group (0.41 ± 0.07) g, 0.37 ± 0.10 g in the MIF alone group and 0.32 ± 0.08 in the MMC alone group (P <0.05) ) g significantly decreased (P <0.01). The mean optical density (OD) of ki-67 expression in combination group was significantly higher than that in control group (0.56 ± 0.04) (P <0.01). Compared with the control group and single MMC group, the mean optical density of MIF group was significantly decreased (P <0.01) There was no significant difference between control group and MMC alone group (P> 0.05). Significant necrosis of the tumor was observed in the combination group. There was no significant difference in the weight of the nude mice in each group (P> 0.05). There was no obvious pathological changes in the main organs of the nude mice. CONCLUSION: Mifepristone in nude mice can reverse the drug resistance of Hela / MMC cells to MMC with no obvious side effects. The reversal of drug resistance may be related to the decrease of the expression of ki-67.