Effect of intratumor heterogeneity of esophageal squamous cell carcinoma on chemotherapy sensitivity
10.3760/cma.j.issn.0253-3766.2017.09.004
- VernacularTitle: 食管鳞状细胞癌癌内异质性与化疗疗效的关系
- Author:
Lei SUN
1
;
Wei WU
1
;
Ming YAN
2
;
Pengli HAN
1
;
Xiang ZHAN
1
;
Xiwen MA
1
;
Xinguang CAO
3
;
Song ZHAO
4
;
Fei GAO
4
;
Yu QI
4
;
Wei CAO
1
Author Information
1. Translational Medical Center, Zhengzhou Central Hospital, Zhengzhou 450007, China
2. Basic Medical College, Zhengzhou University, Zhengzhou 450001, China
3. Endoscopy Center, Henan Cancer Hospital, Zhengzhou 450003, China
4. Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Publication Type:Clinical Trail
- Keywords:
Esophageal squamous cell carcinoma;
Heterogeneity;
Cisplatin;
Chemotherapy sensitivity;
Apoptosis;
Cell cycle
- From:
Chinese Journal of Oncology
2017;39(9):657-663
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship of heterogeneity of esophageal squamous cell carcinoma (ESCC) and chemotherapy sensitivity.
Methods:Five different region specimens isolated from primary tumor(R1~R5)and 1 specimen(R6)isolated from adjacent non-neoplastic tissue from 10 ESCC patients who underwent surgical treatment were cultured in vitro. The inhibitory effect of cisplatin on proliferation of ESCC cells from different regions was determined by methyl thiazolyl tetrazolium (MTT). The cell cycle and apoptosis induced by cisplatin was determined by flow cytometry (FCM) analysis. The mRNA levels of ATP7A and ATP7B were determined by quantitive RT-PCR (qRT-PCR).
Results:The result showed that different regions of each specimen exhibited different chemotherapy sensitivity to cisplatin, and the cell survival rates of region R6 of each specimen were higher than other regions from the same specimen. The cell survival rate of region R3 from the tenth specimen was (81.42±8.84)%, which is significantly higher than (11.90±2.75)% of region R5 (P<0.01). FCM analysis showed that significant differences of early apoptosis and later apoptosis were observed in six specimens induced by cisplatin (P<0.05), and significant differences of cell cycle and G1 period were observed in seven specimens (P<0.05). The qRT-PCR results showed that the mRNA level of ATP7A in region R1, R2, R3, R4 and R5 was (100.00±3.42)%, (118.10±2.21)%, (75.40±4.15)%, (95.40±3.32)% and (41.70±2.57)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7A in region R6 was (175.20±5.32)%, significantly higher than those of regions from R1 to R5 (P<0.05). The mRNA level of ATP7B in region R1, R2, R3, R4 and R5 was (100.00±4.89)%, (73.60±2.65)%, (175.60±6.12)%, (46.10±4.62)% and (363.70±8.67)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7B in region R6 was (1 165.40±7.25)%, significantly higher than those of regions from R1 to R5 (P<0.05).
Conclusion:The intratumor heterogeneity of ESCC results in the heterogeneity of resistance to cisplatin, which affects the chemotherapeutic effect.
