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目的研究叶酸偶联的青霉素G酰化酶(F-PGA)对叶酸受体阳性肿瘤细胞的靶向作用。方法用激光共聚焦显微镜观察宫颈癌HeLa、卵巢癌SKOV3和肺癌A549细胞对F-PGA以及游离叶酸(F-A)的摄取,并进一步用同位素示踪法加以验证和定量检测。结果F-PGA与F-A相似,均能被叶酸受体阳性的HeLa和SKOV3肿瘤细胞选择性摄取,且有饱和性、可逆性、温度依赖性和高亲和性的特点,但不能被叶酸受体阴性的A549细胞摄取。结论F-PGA与F-A都是通过叶酸受体介导,从而特异性地靶向于叶酸受体阳性肿瘤细胞的。
Objective To study the effect of folate-conjugated penicillin G acylase (F-PGA) on folate receptor-positive tumor cells. Methods The uptake of F-PGA and free folate (F-AGA) by cervical cancer HeLa, ovarian cancer SKOV3 and lung cancer A549 cells were observed by laser scanning confocal microscopy and further verified by isotope tracer method. Results F-PGA was similar to FA and was selectively uptake by folate receptor-positive HeLa and SKOV3 tumor cells. It was characterized by saturation, reversibility, temperature dependence and high affinity, but not by folic acid receptor Negative A549 cells uptake. Conclusions Both F-PGA and F-A are specifically mediated by folate receptors to specifically target folate receptor-positive tumor cells.