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背景与目的:临床前和临床研究显示吉西他滨对实体瘤有较好的疗效,尽管已有卵巢癌和红白血病吉西他滨耐药细胞系的报道,但肺癌吉西他滨耐药细胞系尚未见报道。我们建立了人肺腺癌吉西他滨耐药细胞系,并对其细胞生物学特性进行研究。方法:逐步增加培养基中吉西他滨的浓度,建立了对吉西他滨耐药的人肺腺癌细胞系A549-Gem。采用四甲基偶氮唑蓝(MTT)法和集落形成实验,计算出A549和A549-Gem的半数抑制浓度(IC50)和耐药系数(RI)。比较A549和A549-Gem的生长曲线,并计算出两细胞系的倍增时间。采用MTT法检测A549-Gem对几种常用抗肿瘤药物的交叉耐药谱。结果:吉西他滨对A549和A549-Gem的IC50分别为(6.56±1.19)μmol/L和(921.09±225.27)μmol/L,RI为140.52(P=0.0195)。集落形成实验的RI为132.95。根据生长曲线计算出A549和A549-Gem的倍增时间为29.7h和36.4h。交叉耐药实验表明,A549-Gem对长春新碱(VCR)和足叶乙甙(VP-16)的RI分别为54.38和6.18(P<0.01),对阿霉素(ADM)、顺铂(DDP)、阿糖胞苷(Ara-C)和紫杉醇(Taxol)无交叉耐药。结论:成功建立了人肺腺癌吉西他滨耐药细胞系A549-Gem,耐药性能明显、稳定,非常适合用于肺癌中吉西他滨耐药的研究。A549-Gem对VCR、VP-16产生交叉耐药,对ADM、DDP、Ara-C和Taxol无交叉耐药
BACKGROUND & AIM: Preclinical and clinical studies have shown that gemcitabine has a good effect on solid tumors. Gemcitabine-resistant cell lines have not been reported although ovarian cancer and erythroleukemia-resistant gemcitabine-resistant cell lines have been reported. We established a human lung adenocarcinoma-resistant gemcitabine-resistant cell line and studied its cell biology. Methods: The concentration of gemcitabine in the medium was gradually increased, and a human lung adenocarcinoma cell line A549-Gem resistant to gemcitabine was established. The half inhibitory concentration (IC50) and resistance coefficient (RI) of A549 and A549-Gem were calculated by MTT assay and colony formation assay. The growth curves of A549 and A549-Gem were compared and the doubling time of both cell lines was calculated. The cross-resistance spectrum of A549-Gem to several commonly used anti-tumor drugs was detected by MTT assay. Results: The IC50 of gemcitabine on A549 and A549-Gem were (6.56 ± 1.19) μmol / L and (921.09 ± 225.27) μmol / L, respectively. The RI was 140.52 (P = 0.0195). The RI of colony forming experiments was 132.95. According to the growth curves, the doubling time of A549 and A549-Gem was 29.7h and 36.4h respectively. The cross-resistance test showed that the RIs of A549-Gem to vincristine (VCR) and etoposide (VP-16) were 54.38 and 6.18 (P <0.01) DDP), Ara-C and Taxol. CONCLUSION: The human lung adenocarcinoma cell line gemcitabine-resistant cell line A549-Gem has been successfully established, showing obvious and stable drug resistance and is very suitable for the study of gemcitabine resistance in lung cancer. A549-Gem cross-resistance to VCR, VP-16, no cross-resistance to ADM, DDP, Ara-C and Taxol