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目的了解抗表皮生长因子受体(EGFR)单抗对人结肠癌细胞化疗敏感性的影响及其可能的分子机制。方法应用MTT法分别检测伊立替康(CPT-11)、奥沙利铂(L-OHP)、氟尿嘧啶(5-Fu)单药或与抗EGFR单抗(C-225和h-R3)联合应用对人结肠癌细胞株LoVo体外增殖的抑制作用;Western-blotting检测PI3K和Akt蛋白的表达,RT-PCR法检测PI3和AktmRNA表达。结果联合h-R3或C-225均能显著提高伊立替康和草酸铂对LoVo细胞的细胞抑制率;5-Fu与h-R3联合具有类似的协同作用,但与C-225联用时二者之间呈相互拮抗的作用。经C-225或h-R3处理后,LoVo细胞内的PI3K和Akt的表达均明显下调。结论抗EGFR单抗可以增加结肠癌细胞对多数化疗药物的敏感性,这种机制可能与其阻断细胞内PI3K/Akt信号通路有关。
Objective To investigate the effect of anti-epidermal growth factor receptor (EGFR) monoclonal antibody on chemosensitivity of human colon cancer cells and its possible molecular mechanism. Methods MTT assay was used to detect irinotecan (CPT-11), oxaliplatin (L-OHP), fluorouracil (5-Fu) alone or in combination with anti-EGFR monoclonal antibody (C-225 and h-R3). Inhibition of human colon carcinoma cell line LoVo proliferation in vitro; Western-blotting detection of PI3K and Akt protein expression, RT-PCR assay PI3 and Akt mRNA expression. Results Both h-R3 and C-225 could significantly increase the cell inhibition rate of LoVo cells by irinotecan and oxaliplatin; 5-Fu and h-R3 had similar synergistic effects, but when combined with C-225, both Between the antagonistic effect. After treatment with C-225 or h-R3, the expression of PI3K and Akt in LoVo cells was significantly down-regulated. Conclusion The anti-EGFR monoclonal antibody can increase the sensitivity of colon cancer cells to most chemotherapeutic drugs. This mechanism may be related to its blockade of intracellular PI3K/Akt signaling pathway.