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目的:探讨IGF-ⅠR信号旁路是否参与膀胱癌细胞的耐药性。方法:RT-PCR法检测T24膀胱癌细胞和正常尿路上皮细胞IGF-Ⅰ,IGF-Ⅱ及IGF-ⅠRmRNA的表达。流式细胞技术和MTT试验检测反义脱氧寡核苷酸能否增强T24细胞对丝裂霉素药物敏感性及凋亡易感性;免疫印迹技术检测反义脱氧寡核苷酸对T24膀胱癌细胞IGF-ⅠR蛋白表达的影响。结果:IGF-Ⅰ,IGF-Ⅱ及IGG-ⅠRmRNA在无血清培养的T24细胞中高度表达,而正常尿路上皮细胞不表达或仅痕量表达这些生长因子或受体;反义脱氧寡核苷酸阻断IGF-ⅠR通路可以显著抑制膀胱癌细胞的生长并可增强T24细胞对丝裂霉素的敏感性及凋亡易感性。结论:阻断IGF-ⅠR信号通路可有望治疗对化疗不敏感的膀胱癌。
Objective: To investigate whether IGF-IR signaling pathway is involved in the resistance of bladder cancer cells. Methods: RT-PCR was used to detect the expression of IGF-I, IGF-II and IGF-IR mRNA in T24 bladder cancer cells and normal urothelial cells. Flow Cytometry and MTT Assays Assay Anti-Sense Oxidized Deoxyribonucleotide Can Increase the Susceptibility to Apoptosis and Sensitivity of T24 Cells to mitomycin C; Immunoblotting Assay Antisense Oligonucleotide to T24 Bladder Cancer Cells The effect of IGF-IR protein expression. RESULTS: IGF-I, IGF-II and IGG-IR mRNA were highly expressed in serum-free cultured T24 cells, whereas normal urothelial cells did not express or only expressed these growth factors or receptors in trace amounts; antisense oligodeoxynucleotides Acid blocking IGF-IR pathway can significantly inhibit the growth of bladder cancer cells and enhance the sensitivity of T24 cells to mitomycin and apoptosis susceptibility. Conclusion: Blockade of IGF-IR signaling pathway may be expected to treat chemotherapy-insensitive bladder cancer.