拓普替康耐药卵巢癌细胞基因的表达变化及意义

Significance of gene expression aleration in topotecan-resistance ovarian carcinoma ceil line

目的探讨人卵巢癌获得性拓普替康(TPT)耐药的相关基因。方法采用大剂量间歇诱导法,用拓普替康(TPT)反复冲击诱导培养人卵巢癌SKOV 3细胞株,建成SKOV 3/TPT耐药株。用A ffym etrix人类基因组U 133A基因表达谱芯片,比较SKOV 3/TPT及SKOV 3细胞基因表达的差异。选择高表达的基因进行RT-PCR验证。结果基因芯片检测发现,二者有283种基因表达有显著性差异。有7个差异表达基因可能参与了SKOV 3/TPT细胞的耐药机制,其中上调最明显的基因为M RP 3,其次为M RP 7、钠离子通道蛋白及固醇异构酶基因;明显下调的基因有M RP 4、假设蛋白和免疫球蛋白基因。RT-PCR检测M RP 3 mRNA在耐药细胞中呈高表达,与基因芯片结果一致。结论M RP 3、M RP 4、M RP 7、钠离子通道蛋白、固醇异构酶、假设蛋白和免疫球蛋白基因为人卵巢癌获得性TPT耐药相关基因。

[Objective] To identify the molecular qene of acquired topotecan-resistance ovarian carcinoma. [Methods] founded With the corresponding dose revulsion,Topotecan-resistant cell subline （SKOV3/TPT） was Expression profiles between the SKOV3/TPT and SKOV3 was compared with Affymetrix human U133A gene chips. RT-PCR were performed to tested the transcription level of MRP3 gene. [Results] Gene chip revealed that 7 resistant genes were differential expressed between SKOV3/TPT and SKOV3 cells. MRP3, MRP7,SCNllA and EBP were overexpressed and MRP4,FIJ12443 and SEMA3C were underexpressed in SKOV3/TPT cells. RTPCR demonstrated that overexpression of MRP3 in SKOV3/TPT cells,but not in SKOV3 cells. [Conclusion] MRP3, MRP4, MRP7, SCN llA EBP FIJ12443 and SEMA3C gene are involved in acquired topotecan-resistant ovarian cancer.