紫杉醇联合顺铂化疗对人卵巢浆液性囊腺癌组织occludin和ZO-1表达以及线粒体超微结构的影响

 目的：观察紫杉醇联合顺铂化疗对人卵巢浆液性囊腺癌（serous cystadenocarcinoma, SC）组织紧密连接蛋白occludin和zonula occludens-1(ZO-1)表达以及线粒体超微结构的影响。方法：取紫杉醇联合顺铂化疗和未化疗的卵巢癌患者SC组织，用电镜观察其线粒体超微结构，用免疫组织化学法观察癌组织occludin和ZO-1蛋白的表达，并以子宫肌瘤患者的正常卵巢组织为正常对照。结果：SC细胞线粒体明显肿胀，呈现巨线粒体，且嵴断裂十分显著；化疗后的SC细胞线粒体肿胀减轻，形态接近正常。SC细胞较正常卵巢上皮细胞occludin和ZO-1蛋白表达明显降低（P<005或P<001）；化疗组较未化疗组SC细胞occludin和ZO-1蛋白表达明显增多（P<001）。结论: 紧密连接蛋白occludin 和 ZO-1的低表达可能是SC浆液生成增多和细胞代谢异常的关键所在，而化疗可促进紧密连接蛋白表达，从而减轻线粒体结构肿胀并改善细胞功能。

Effects of paclitaxel-cisplatin combination chemotherapy on expression of occludin and ZO-1 proteins and mitochondrial ultrastructure in human ovarian serous cystadenocarcinoma tissues

AIM：To investigate the effects of paclitaxel-cisplatin combination chemotherapy on the expression of tight junction proteins, occludin and zonula occludens-1 (ZO-1), and the ultrastructural changes of mitochondria in human ovarian serous cystadenocarcinoma (SC). METHODS：Paraffin-embedded SC specimens from 20 cases of ovarian carcinoma patients were obtained by carcinectomy after paclitaxel-cisplatin combination chemotherapy (n=10) or without chemotherapy (n=10). Ovarian tissues from 3 cases of uterine leiomyoma patients served as normal controls. The ultrastructure of mitochondria was observed under electron microscope, and the protein expression of occludin and ZO-1 was determined by immunohistochemistry. RESULTS：Significant mitochondrial swelling, giant mitochondria and disorganized cristae in SC cells were observed under electron microscope, while the ultrastructural changes of mitochondria returned to nearly normal after chemotherapy. The expression levels of occludin and ZO-1 in SC cells were significantly lower than those in normal ovarian epithelial cells (P<005 or P<001), while those in chemotherapy group were significantly increased compared with non-chemotherapy group (P<005). CONCLUSION: The low expression of tight junction proteins may be the key to increased serous fluid and metabolic abnormalities in SC. Chemotherapy promotes the expression of tight junction proteins, thus reducing mitochondrial swelling and improving the function of cells.