Triptolide reverses apatinib resistance in gastric cancer cell line MKN45 via inhibition of heat shock protein 70
10.3760/cma.j.issn.0253-3766.2018.02.003
- VernacularTitle: 雷公藤内酯抑制热休克蛋白70逆转MKN45胃癌细胞阿帕替尼耐药
- Author:
Fei TENG
1
;
Zhiyuan XU
2
;
Hang LYU
3
;
Yiping WANG
3
;
Lijing WANG
4
;
Ting HUANG
1
;
Jiancheng SUN
1
;
Haote ZHU
1
;
Yixiu NI
1
;
Xiangdong CHENG
2
Author Information
1. The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
2. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
3. Central Laboratory, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diagnosis and Treatment of Digestive System Tumor, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
4. Department of Medical Imaging, Zhejiang Provincial Tumor Hospital, Hangzhou 310022, China
- Publication Type:Journal Article
- Keywords:
Stomach neoplasms;
Triptolide;
Heat shock protein;
Apatinib;
Drug resistance
- From:
Chinese Journal of Oncology
2018;40(2):92-98
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of triptolide, a specific inhibitor of heat shock protein 70 (HSP70), on apatinib resistance in gastric cancer cells line MKN45.
Methods:The apatinib-resistant cells (MKN45/AR) and MKN45 parental cells were treated with apatinib, triptolide and apatinib combined with triptolide, respectively. CCK-8 assay was performed to determine the half maximal inhibitory concentration (IC50) of MKN45/AR and MKN45 cells in the presence of different treatment. The mRNA expression of heat shock protein gene (HSPA1A and HSPA1B) was detected by RT-PCR, while the protein expression of heat shock protein 70 was analyzed using Western blot in MKN45/AR and MKN45 cells.
Results:The IC50 values of apatinib-sensitive and apatinib-resistant MKN45 cells were 10.411 μmol/L and 70.527 μmol/L, respectively, showing a significant difference (P<0.05). The mRNA expression of HSPA1A and HSPA1B in MKN45/AR cells was significantly higher than that in MKN45 cells (P<0.001). The protein expression of heat shock protein 70 was significantly decreased after 0.25 μmol/L triptolide treatment in MKN45/AR cells (P<0.01). When heat shock protein 70 was inhibited by triptolide, the IC50 value of apatinib in MKN45/AR cells was reduced to 11.679 μmol/L, which was significantly lower than cells treated with apatinib alone (P<0.05).
Conclusions:The apatinib-resistant MKN45 cells have high levels of heat shock protein 70. Low doses of triptolide can significantly inhibit heat shock protein 70, leading to reverse the resistance phenotype of MKN45/AR cells. Therefore, inhibition of heat shock protein 70 provides a new therapy strategy for patients with apatinib resistance.
