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目的 建立宫颈癌Hela MMC耐药细胞亚系 ,并探讨其耐药机制。方法 以人宫颈癌Hela细胞为亲本 ,采用丝裂霉素连续性药物作用 ,间隙性增加药量 ,逐步提高药物浓度的方法 ,分离出MMC耐药亚系(Hela MMC) ,并比较两种细胞生物学特性差异。结果 Hela MMC细胞对MMC有 5.0 2倍耐药 ,对DDP有2 .0 3倍交叉耐药 ,对VCR、ADM和 5 Fu保持敏感 ;耐药细胞核分裂指数增加 ;耐药细胞内丝裂霉素蓄积量比亲代细胞低 32 .64% (P <0 .0 1)。DNA链间交联指数降低 51.91% (P <0 .0 1)。结论 耐药细胞Hela MMC具有多药耐药特性且生长增殖能力强于亲代细胞 ,其对MMC耐药性与细胞内药物浓度降低和DNA链间交联减少有关。
Objective To establish a cervical cancer Hela MMC-resistant cell line and explore its resistance mechanism. Methods Human cervical cancer Hela cells were used as the parent, and mitomycin C was used as a continuous drug to increase the drug dose, and the drug concentration was gradually increased. The MMC resistant subline (Hela MMC) was isolated and the two cells were compared. Differences in biological characteristics. Results Hela MMC cells were 5.02-fold resistant to MMC, had 2. 0 3-fold cross-resistance to DDP, remained sensitive to VCR, ADM, and 5 Fu; the nuclear index of drug-resistant cells increased; drug-resistant intracellular mitomycins The accumulation was 32.64% lower than that of the parental cells (P < 0.01). The index of cross-linking between DNA strands decreased by 51.91% (P < 0.01). Conclusion The drug-resistant Hela MMC possesses multidrug resistance and its growth and proliferation ability is stronger than that of the parental cells. Its resistance to MMC is related to the decrease of intracellular drug concentration and the reduction of DNA interstrand cross-linking.