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目的考察抗表皮生长因子受体全人单克隆抗体Ranti-HER单用及联合用药对裸鼠人癌移植瘤的抑制作用,探讨其抑制作用是否与表皮生长因子受体(epidermal growth factor receptor,EGFR)表达有关。方法采用流式细胞术定性人源肿瘤细胞EGFR的表达程度,建立人源肿瘤细胞裸鼠皮下移植瘤模型,然后分组给药,以相对肿瘤增值率评估其抗肿瘤有效性。结果人鳞状细胞癌A431细胞为EGFR高表达细胞,人结肠癌HT29和SW948细胞对EGFR低表达,人结肠癌SW620细胞对EGFR为阴性表达。给予不同剂量Ranti-HER(0.25、0.5、1 mg·只-1,biw×3)能显著抑制A431移植瘤的生长,并表现出一定的剂量相关性;与多柔比星(125μg·只-1,qd×2)合用后呈现联合抗肿瘤作用。Ranti-HER 1.0 mg(biw×3)能明显延缓SW948移植瘤的生长,与伊立替康联合应用,抑制肿瘤生长作用表现出相加的趋势。对于HT29和SW620移植瘤,Ranti-HER1.0 mg(biw×3)未见明显抑瘤作用。结论 Ranti-HER单独应用能抑制裸鼠人癌移植瘤的生长,其抑制作用与EGFR的表达水平有一定相关性,Ranti-HER与其他化疗药物联合应用,具有协同抗肿瘤作用。
Objective To investigate the inhibitory effect of anti-epidermal growth factor receptor monoclonal antibody Ranti-HER alone or in combination on the growth of human xenografts in nude mice and to investigate whether its inhibitory effect is related to the expression of epidermal growth factor receptor (EGFR ) Expression. Methods Flow cytometry was used to characterize the expression of EGFR in human tumor cells. A subcutaneous xenograft tumor model of human tumor cells was established in nude mice and then administered in groups. The anti-tumor efficacy was evaluated by relative tumor proliferation rate. Results Human squamous cell carcinoma A431 cells were EGFR highly expressed cells, human colon cancer HT29 and SW948 cells had low EGFR expression, and human colon carcinoma SW620 cells were negative for EGFR. Ranti-HER (0.25, 0.5, 1 mg · kg -1, biw × 3) could significantly inhibit the growth of A431 xenografts and showed a certain dose-dependent relationship with the dosage of doxorubicin (125 μg · pg / 1, qd × 2) showed a combination of anti-tumor effect. Ranti-HER 1.0 mg (biw × 3) can significantly delay the growth of SW948 xenografts, and combined with irinotecan can inhibit the growth of tumors and show an additive trend. For HT29 and SW620 xenografts, no significant anti-tumor effect was observed with Ranti-HER1.0 mg (biw × 3). Conclusion Ranti-HER alone can inhibit the growth of human xenografts in nude mice. The inhibitory effect of Ranti-HER is related to the expression of EGFR. Ranti-HER has synergistic anti-tumor effect with other chemotherapeutic agents.