TRAIL-induced apoptosis of ovarian cancer cell lines with selective drug resistance
TRAIL-induced apoptosis of ovarian cancer cell lines with selective drug resistance
复制标题
DOI：
10.1055/s-2005-872998
复制
发表时间：
2005-11-01
影响因子：
2.7
通讯作者：
Bauknecht, T
中科院分区：
文献类型：
--
作者：
Meinhold-Heerlein, I;Borges-Engeby, K;Bauknecht, T
化疗耐药仍然是晚期卵巢癌治疗中的一个关键问题。各种药物组合的使用已成功地提高了治疗反应和无复发生存率。尽管如此，大多数卵巢癌会复发，并不断产生耐药性。肿瘤坏死因子相关的凋亡诱导配体(TRAIL)与铂类、紫杉烷等多种细胞抑制药物联合应用，在组织培养模型中显示出协同作用，用于治疗不同来源的癌细胞。本研究旨在探讨TRAIL能否诱导耐药卵巢癌细胞株的凋亡和/或生长抑制。为了建立具有选择性耐药的卵巢癌细胞株，将亲本细胞株HY分别用增加药物浓度的顺铂、依托泊苷、多西紫杉醇和紫杉醇处理。用福尔马赞WST-1法(ROCHE)检测细胞生长抑制，用细胞死亡检测ELISA法(ROCHE)检测细胞凋亡。TRAIL处理后，所有耐药细胞株均表现出生长抑制和细胞凋亡。除了顺铂耐药细胞株与亲本细胞株反应相似外，所有其他耐药细胞株的TRAIL反应明显弱于亲本细胞株。顺铂耐药细胞反应最多，多西紫杉醇耐药细胞反应最小。与亲本细胞相比，TRAIL耐药细胞在不同的细胞抑制药物作用下表现出较少的生长抑制和较少的细胞凋亡。抗细胞药物和TRAIL的协同作用以及耐药卵巢癌细胞对TRAIL的反应提示TRAIL可作为治疗晚期卵巢癌的一种选择。
Chemotherapy resistance remains a key problem in the treatment of advanced ovarian cancer. Usage of various drug combinations has been successful to improve therapy response and relapse-free survival. Nonetheless, the majority of ovarian cancers relapse, consecutively developing drug resistance. The combination of TRAIL (TNF-Related Apoptosis Inducing Ligand) and various cytostatic drugs such as platin derivates and taxanes has shown synergistic effects in tissue culture models when cancer cell lines of different origins were treated. Our study was performed to evaluate whether TRAIL can cause apoptosis and/or growth inhibition of chemotherapy-resistant ovarian cancer cell lines. To develop ovarian cancer cell lines with selective drug resistance, the parental cell line HEY was treated with increasing drug concentrations of cisplatin, etoposide, docetaxel, and paclitaxel, respectively. Growth inhibition was evaluated with the formazan-based WST-1 assay (Roche); apoptosis induction was evaluated with the Cell Death Detection ELISA (Roche). All resistant cell lines showed growth inhibition and apoptosis when treated with TRAIL. Apart from the cisplatin-resistant cell line, which responded almost similarly compared to the parental cell line, the TRAIL response of all other resistant cell lines was significantly weaker than of the parental cell line. Cisplatin-resistant cells showed the most, docetaxel-resistant cells the least response. TRAIL-resistant cells showed less growth inhibition as well as less apoptosis than parental cells when treated with different cytostatic drugs. The synergistic effects of cytostatic drugs and TRAIL and the response of chemoresistant ovarian cancer cells to TRAIL suggest TRAIL can be a therapeutic option for the treatment of advanced ovarian cancer.