van der Zee A G, van Ommen B, Meijer C, Hollema H, van Bladeren P J, de Vries E G
Department of Gynaecology, University Hospital, Groningen, Netherlands.
Br J Cancer. 1992 Nov;66(5):930-6. doi: 10.1038/bjc.1992.388.
Glutathione S-transferase (GST) isoenzyme composition, isoenzyme quantities and enzymatic activity were investigated in benign (n = 4) ovarian tumours and malignant ovarian tumours, before (n = 20) and after (n = 16) chemotherapy. Enzymatic activity of GST in cytosols was measured by determining 1-chloro-2,4-dinitrobenzene conjugation with glutathione, cytosolic GST subunits were determined by wide pore reversed phase HPLC, using a S-hexylglutathione-agarose affinity column, and isoelectric focussing. Both GST activity and GST pi amount were not related to histopathologic type, differentiation grade, or tumour volume index in untreated malignant tumours. GST isoenzyme patterns were identical in benign tumours and malignant tumours before and after platinum/cyclophosphamide chemotherapy, while GST pi was the predominant transferase. Mean GST activity and GST pi amount were decreased (P < 0.05) in malignant ovarian tumours after platinum/cyclophosphamide chemotherapy compared to untreated ovarian malignant tumours. No relation was found in untreated ovarian tumours between GST pi amount and response to platinum/cyclophosphamide chemotherapy. Thus, within the limitations of the current study no arguments were found for a role of GST in in vivo drug resistance of malignant ovarian tumours to platinum/cyclophosphamide chemotherapy.
研究了良性(n = 4)卵巢肿瘤以及恶性卵巢肿瘤在化疗前(n = 20)和化疗后(n = 16)的谷胱甘肽S-转移酶(GST)同工酶组成、同工酶数量及酶活性。通过测定1-氯-2,4-二硝基苯与谷胱甘肽的结合来测量胞质溶胶中GST的酶活性,使用S-己基谷胱甘肽-琼脂糖亲和柱和等电聚焦,通过宽孔反相高效液相色谱法测定胞质溶胶中的GST亚基。在未经治疗的恶性肿瘤中,GST活性和GST π含量均与组织病理学类型、分化程度或肿瘤体积指数无关。在铂/环磷酰胺化疗前后,良性肿瘤和恶性肿瘤中的GST同工酶模式相同,而GST π是主要的转移酶。与未经治疗的卵巢恶性肿瘤相比,铂/环磷酰胺化疗后恶性卵巢肿瘤的平均GST活性和GST π含量降低(P < 0.05)。在未经治疗的卵巢肿瘤中,未发现GST π含量与对铂/环磷酰胺化疗的反应之间存在关联。因此,在当前研究的局限性内,未发现支持GST在恶性卵巢肿瘤对铂/环磷酰胺化疗的体内耐药性中起作用的证据。