| 陈虎 农晓琳 陈宇麟 李佳荃.顺铂短期诱导人腺样囊性癌细胞NACC 产生耐药性的研究[J].现代生物医学进展英文版,2016,16(14):2641-2645. |
| 顺铂短期诱导人腺样囊性癌细胞NACC 产生耐药性的研究 |
| Induction of Drug Resistance in NACC Cells by Transient Exposure toCisplatin |
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| DOI： |
| 中文关键词: NACC 细胞 顺铂 Survivin ERCC1 |
| 英文关键词: NACC cell line Cisplatin Survivin ERCC1 |
| 基金项目:国家自然科学基金项目(81360404)；广西自然科学基金项目(2013GXNSFAA019231) |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| Objective:To study the effect of transient exposure to cisplatin on drug resistance of novel human palatal salivary
gland cell line of adenoid cystic carcinoma (NACC) and the mechanism of drug resistance.Methods:The DDP-resistant cell line
NACC/DDP3 was established by constant-dose cisplatin intermittent selection from its parental cell NACC. The resistance index was
determined by MTT, the mRNA expression of Survivin and ERCC1 was analyzed by real-time quantitive PCR. Tumor cells were injected
subcutaneously in the right axillary of nude mice, the xenografting mice were randomly divided into the control group and 2 mg·kg-1
DDP treated group after volume of solid tumors reached 0.5 cm3, tumor growth inhibition rates of 2 mg·kg-1 DDP on xenografting mice
were compared, then the tumor samples were stained by hematoxylin-eosin (HE) after the tumors were excised.Results:Compared with
NACC cells, the NACC/DDP3 cells showed significantly higher drug-resistance, the resistance index was 1.44, the mRNA expression of
Survivin and ERCC1 in NACC/DDP3 was also augmented, the expression level of Survivin and ERCC1 in NACC/DDP3 was 2.02 (P<0.
01) and 1.59 (P<0.05) fold of NACC, respectively. The xenografting mice of NACC group treated with DDP at 2 mg·kg-1 showed
significantly higher tumor growth inhibition[(31.64± 1.15) %at day 30] than NACC/DDP3 group[(16.66± 0.76) %at day 30](P<0.01).
Two group samples were histologically similar to the phenotype of the solid type of adenoid cystic carcinoma (ACC).Conclusion:The
phenotype of drug-resistance of NACC can be induced by transient exposure to cisplatin, the drug-resistance of NACC/DDP3 might
related to the over expression of mRNA of Survivin and ERCC1. The subcutaneous xenograft of NACC/DDP3 can provide an ideal
model for reversing cisplatin resistance of ACC in vivo for the NACC/DDP3 maintained the drug-resistance phenotype when inoculated
into nude mice. |
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