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目的:探讨人腭部涎腺腺样囊性癌细胞(NACC)经顺铂(DDP)短期诱导后耐药性产生情况及耐药机制。方法:采用恒定浓度DDP反复间歇诱导法诱导NACC细胞,获得耐药细胞NACC/DDP3,MTT法检测细胞耐药指数;实时荧光定量PCR检测存活蛋白(Survivin)及核苷酸切除修复交叉互补基因1(ERCC1)的mRNA表达;裸鼠右侧腋部皮下接种NACC及NACC/DDP3细胞,成瘤后将荷瘤裸鼠随机分为生理盐水对照组和DDP 2 mg·kg~(-1)组,比较2 mg·kg~(-1) DDP对两组荷瘤裸鼠的抑瘤率,HE染色观察肿瘤组织形态。结果:诱导后的NACC/DDP3对DDP耐药性增强,耐药指数为1.44;在NACC/DDP3细胞中,Survivin及ERCC1的mRNA表达明显上调,分别为亲本细胞的2.02(P<0.01)和1.59(P<0.05)倍;2 mg·kg~(-1) DDP对NACC组抑瘤率为(31.64±1.15)%,对NACC/DDP3组抑瘤率为(16.66±0.76)%,两组间差异具有统计学意义(P<0.01),HE染色观察两组瘤体标本均符合腺样囊性癌实体型组织学表现。结论:NACC细胞经DDP短期诱导即产生一定耐药性,NACC/DDP3细胞中Survivin及ERCC1的mRNA表达上调,提示Survivin及ERCC1可能参与了腺样囊性癌细胞对DDP的耐药。相同剂量DDP对NACC/DDP3所建立的皮下移植瘤模型抑瘤率显著低于NACC组,提示NACC/DDP3接种到裸鼠体内仍具有耐药性,这将为体内研究耐药腺样囊性癌的治疗提供良好的平台。
OBJECTIVE: To investigate the drug resistance and mechanism of resistance induced by short-term induction of cisplatin (DDP) in human palatal salivary adenoid cystic carcinoma cells (NACC). Methods: NACC cells were induced by repeated intermittent induction of DDP at a constant concentration, and drug-resistant cells NACC / DDP3 were obtained by MTT assay. Survivin and nucleotomy were detected by real-time fluorescence quantitative PCR (NCC) and NACC / DDP3 cells were inoculated subcutaneously in the right axilla of nude mice. The nude mice bearing tumor were randomly divided into normal saline control group and DDP 2 mg · kg -1 group, The inhibitory rates of 2 mg · kg -1 DDP on tumor-bearing nude mice in two groups were compared. The morphology of tumor was observed by HE staining. Results: The resistance of NACC / DDP3 to DDP was enhanced and the resistance index was 1.44. The mRNA expressions of Survivin and ERCC1 were significantly up-regulated in NACC / DDP3 cells as 2.02 (P <0.01) and 1.59 (P <0.05). The inhibitory rate of 2 mg · kg -1 DDP on NACC was (31.64 ± 1.15)%, and that on NACC / DDP3 was (16.66 ± 0.76)%, The differences were statistically significant (P <0.01). The HE staining showed that the histological specimens of both groups were consistent with the histological findings of adenoid cystic carcinoma. CONCLUSIONS: NACC cells induced by DDP for a short period of time have a certain drug resistance, and the mRNA expression of Survivin and ERCC1 is up-regulated in NACC / DDP3 cells, which suggests Survivin and ERCC1 may be involved in the resistance of adenoid cystic carcinoma cells to DDP. The same dose of DDP on NACC / DDP3 established subcutaneous xenograft model tumor inhibition rate was significantly lower than the NACC group, suggesting that NACC / DDP3 inoculated into nude mice still resistant, which will be the study of drug-resistant adenoid cystic carcinoma The treatment provides a good platform.