Okuma Yoshiaki, Kiguchi Kazushige, Koshitaka Yutaka, Okamura Asami, Ishiwata Isamu, Kondo Haruhiro, Ishizuka Bunpei, Tadokoro Mamoru
Department of Obstetrics and Gynecology, St. Marianna University School of Medicine.
Hum Cell. 2003 Sep;16(3):131-9. doi: 10.1111/j.1749-0774.2003.tb00145.x.
Despite recent advances in the application of chemotherapy to ovarian cancer, the development of alternative therapies that retain activity against drug-resistant-tumors remains a high priority. We analyzed a number of cultured ovarian cancer cell lines of different tissue types for the presence or absence of sensitivity to various anticancer drugs as well as expression patterns of oncogene products (erbB-2, EGFR, bcl-2). As a result, we identified oncogene products that were related to resistance. Using 9 cultured cell lines of ovarian cancers (serous, mucinous, endometrioid, clear, undifferentiated), sensitivities to anticancer drugs were investigated using the MTT assay. The phenotypes of oncogene products expressed by the above cultured cell lines were analyzed by Western blotting. The oncogene products involved in resistance to anticancer drugs were identified by multivariate analysis. Positive correlation between the resistance to anticancer drugs and the oncogene products was obtained by multivariate analysis for (a) CDDP and erbB-2 (b) x p-16 and erbB-2, and (c) MMC and EGFR. Correlation between resistance to anticancer drugs and expression of certain oncogene products was obtained in ovarian cancers, suggesting that sensitivity to anticancer drugs could be predicated prior to chemotherapy.
尽管在卵巢癌化疗应用方面取得了最新进展，但开发对耐药肿瘤仍具有活性的替代疗法仍然是当务之急。我们分析了多种不同组织类型的培养卵巢癌细胞系，以确定它们对各种抗癌药物的敏感性以及癌基因产物（erbB-2、表皮生长因子受体、bcl-2）的表达模式。结果，我们鉴定出了与耐药性相关的癌基因产物。使用9种培养的卵巢癌细胞系（浆液性、黏液性、子宫内膜样、透明、未分化），采用MTT法研究其对抗癌药物的敏感性。通过蛋白质印迹法分析上述培养细胞系所表达的癌基因产物的表型。通过多变量分析鉴定出参与抗癌药物耐药性的癌基因产物。通过对（a）顺铂和erbB-2、（b）xp-16和erbB-2以及（c）丝裂霉素和表皮生长因子受体进行多变量分析，得出抗癌药物耐药性与癌基因产物之间呈正相关。在卵巢癌中发现抗癌药物耐药性与某些癌基因产物的表达之间存在相关性，这表明在化疗前可以预测对抗癌药物的敏感性。
