RG-14260增强子宫内膜癌细胞化疗敏感性研究

Experimental of RG-14260 on Improving Chemosensitivity of Human Endometrial Carcinoma Cells in vitro

摘要:

目的: 研究酪氨酸磷酸化抑制剂RG-14260(RG)单独或联合阿霉素、顺铂及紫杉醇对子宫内膜癌ishikawa细胞增殖的影响,为临床应用RG治疗子宫内膜癌提供理论依据。 方法: 应用10 μmol ·L^-1RG 与各1/2的IC₅₀量的阿霉素(ADM)、顺铂(DDP)及紫杉醇(PTX)联合,MTT法检测细胞增殖抑制率;RT-PCR法检测RG、阿霉素、顺铂及紫杉醇对细胞表皮生长因子受体EGFRmRNA表达影响; Western blot法检测10 μmol ·L^-1RG 作用6,12,24 h后细胞p21蛋白表达水平。 结果: RG可显著降低细胞EGFR 基因mRNA水平,上调p21蛋白表达。 结论: RG通过抑制EGFR信号通路,上调p21蛋白表达,增强化疗药物对子宫内膜癌细胞的杀伤作用。

Abstract:

Objective: To investigate the effect of RG-14260 on the proliferation and drug sensitivity of human endometrial carcinoma line ishikawa cells in vitro. Method: Cell proliferation inhibition rate of ishikawa cells was determined using MTT method after treatment with half of the IC₅₀of the ADR,DDP,PTX and 10 μmol ·L^-1RG alone or combination for 24 h. The mRNA levels of EGFR after treatment with RG and drug alone was detected by RT-PCR. Western blot was used to measured p21 protein abundance after treatment with 10 μmol ·L^-1RG for 6,12,24 h. Result: RG-14260 significantly decreased the mRNA expressions of EGFR and increased the abundance of p21 protein. Compared with the treatment with agents alone, combined treatment of the RG-14260 significantly increased cell proliferation inhibition rate and improved the cytotoxicity of the chemotherapeutic agents(P<0.05). Conclusion: RG-14260 can block the EGFR pathway and increase p21 protein to inhibit the proliferation and enhance the chemosensitivity of human endometrial carcinoma ishikawa cells.