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 G(1) 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.