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多西环素增加卵巢癌细胞HO8910对顺铂化疗敏感性
吴薇1,2△,余立华2△,马蓓2*,徐明娟1*
0
(1. 第二军医大学长海医院妇产科,上海 200433
2. 第二军医大学基础部生理学教研室,上海 200433
共同第一作者
*通信作者)
摘要:
目的 探讨多西环素对卵巢癌的抗肿瘤作用及可能机制。 方法 采用MTT方法检测多西环素单独作用及与顺铂联合用药时对卵巢癌细胞HO8910增殖的影响;采用RT-RCR检测卵巢癌细胞HO8910中CXCR4 mRNA的表达;采用蛋白质免疫印迹法检测多西环素作用后卵巢癌细胞HO8910中CXCR4表达的改变。结果 较低浓度多西环素(10 μg/mL)作用48 h后即可抑制卵巢癌细胞HO8910的增殖活力(P<0.01),当其浓度为50 μg/mL时抑制率达(70±2)%。多西环素与顺铂联合用药后对癌细胞的抑制效应大于同一浓度顺铂单独作用时,可提高癌细胞对顺铂的化疗敏感性。多西环素抑制卵巢癌细胞HO8910中CXCR4的表达。结论 多西环素对卵巢癌细胞HO8910有明确的抑制增殖作用,能增加癌细胞对顺铂化疗的敏感性。SDF-1/CXCR4通路可能参与其中。
关键词:  多西环素  卵巢肿瘤  CXCR4受体  顺铂  肿瘤抗药性
DOI:10.3724/SP.J.1008.2013.00612
投稿时间:2013-03-21修订日期:2013-04-23
基金项目:上海市科委基金(10411960100);中国癌症基金会(E12012006).
Doxycycline increases chemosensitivity of ovarian cancer HO8910 cells to cisplatin
WU Wei 1,2△,YU Li-hua2△,MA Bei2*,XU Ming-juan1*
(1. Department of Gynecology and Obstetrics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
2. Department of Physiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China

Co-first authors.
*Corresponding authors.)
Abstract:
Objective To investigate the anti-tumor effect of doxycycline against ovarian cancer cells and the underlying mechanism. Methods MTT assay was used to test the tumor cell viability after treated with doxycycline alone or in combination with cisplatin. RT-RCR was used to examine CXCR4 mRNA expression in HO8910 cells. Western blotting analysis was used to determine CXCR4 protein expression after doxycycline treatment. Results Treatment with low dose of doxycycline (10 μg/mL) for 48 hours notably inhibited the proliferation of ovarian cancer cell HO8910 (P<0.01), with the inhibition rate being (70±2)% when doxycycline concentration was at 50 μg/mL. Doxycycline combined with cisplatin had greater inhibitory effect against HO8910 cells compared with cisplatin alone at the same concentration. Doxycycline treatment down-regulated CXCR4 expression in HO8910 cells. Conclusion Doxycycline has a definite inhibitory effect against proliferation of ovarian cancer HO8910 cells, and it can increase the sensitivity of tumor cells to cisplatin, which may involve SDF-1/CXCR4 signaling pathway.
Key words:  doxycycline  ovarian neoplasms  CXCR4 receptors  cisplation  neoplasm drug resistance