A novel chemo-resistant gene MSX2 discovered by establishment of two pancreatic cancer drug resistant cell lines JF305/CDDP and PANC-1/GEM
10.3760/cma.j.issn.0253-3766.2018.05.003
- VernacularTitle: 胰腺癌耐药细胞株JF305/CDDP和PANC－1/GEM的生物学特性及新耐药相关基因MSX2的发现
- Author:
Wei YUAN
1
;
Chenguang SUI
1
;
Xiao MA
1
;
Jie MA
2
Author Information
1. State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
2. Department of Biotherapy, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
- Publication Type:Journal Article
- Keywords:
Pancreatic neoplasms;
Drug resistance;
Cell line;
MSX2;
MRP2
- From:
Chinese Journal of Oncology
2018;40(5):330-334
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore new multidrug resistant genes of pancreatic cancer by establishment and characterization of chemo-resistant cell lines.
Methods:The cisplatin-resistant cell line JF305/CDDP and the gemcitabine-resistant cell line PANC-1/GEM were induced by high-dose intermittent treatment. CCK-8 assay was used to detect the 50% inhibiting concentration (IC50), drug resistance index (R), cross-resistance, and growth difference of different cells. The changes of cell cycle and migration ability of drug-resistant cells were determined by flow cytometry and transwell assay, respectively. And then real-time fluorescence quantitative PCR was used to detect the expression of multidrug resistance-related genes.
Results:The drug resistance indexes of JF305/CDDP and PANC-1/GEM were 15.3 and 27.31, respectively, and there was cross-resistance. Compared with the parental cells, the proliferation rate of JF305/CDDP was decreased by 40% on the fourth day (P<0.05); the proportion of S phase was decreased from (45±2)% to (30±2)% (P<0.05), and the migration ability was enhanced from (32 ±1) cells per field to (158±5) cells per field (P<0.01). The expression of multidrug resistance-related genes MRP2, MDR1, LRP and MSX2 was increased in JF305/CDDP cells (P<0.05). Knockdown of MSX2 in JF305 cells reduced the expression of MRP2, whereas overexpression of MSX2 in PANC-1 cells upregulated MRP2 level (P<0.05).
Conclusions:Two stable multidrug resistant cell lines of pancreatic cancer, JF305/CDDP and PANC-1/GEM, were successfully established. MSX2 might be a new drug resistance related gene in pancreatic cancer cells by up-regulation of MRP2 expression.
