Effect of intratumor heterogeneity of esophageal squamous cell carcinoma on chemotherapy sensitivity / 中华肿瘤杂志

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.