Response to microtubule-interacting agents in primary epithelial ovarian cancer cells.
Response to microtubule-interacting agents in primary epithelial ovarian cancer cells.
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DOI：
10.1186/1475-2867-13-33
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发表时间：
2013-04-10
影响因子：
5.8
通讯作者：
Shahabi S
中科院分区：
文献类型：
--
作者：
Pellicciotta I;Yang CP;Venditti CA;Goldberg GL;Shahabi S
卵巢癌占女性所有癌症的近4%，是西方世界妇科恶性肿瘤死亡的主要原因。标准的一线辅助化疗治疗包括紫杉醇（Taxol）和铂类药物。紫杉醇、埃博霉素B（Epo B）和discodermolide属于抗肿瘤剂家族，其特异性干扰微管并将细胞阻滞在细胞周期的G2/M期。尽管化疗治疗取得了初步成功，但许多患者因化疗耐药性而复发。体外建立卵巢癌原代细胞系为更好地了解卵巢癌耐药机制提供了有力的工具。我们描述了上皮性卵巢癌患者腹水中原发性卵巢癌细胞的产生和特征。检测这些细胞系对紫杉醇、EpoB和discodermolide的化学敏感性，并将细胞周期分析与永生化卵巢癌细胞系SKOV 3和Hey的细胞周期分析进行比较。同时探讨了αβ-微管蛋白和p53状态与耐药的关系。所有新产生的原代癌细胞对药物高度敏感。在所有检测的原代细胞系中均未发现αβ-微管蛋白突变。然而，在残基72处具有p53突变（Arg至Pro）的一种细胞系对所有药物治疗均表现出改变的细胞周期谱。与原发性卵巢癌细胞相比，永生化卵巢癌细胞对EpoB治疗的反应不同，p53多态性提示患者抗肿瘤反应的临床意义。从卵巢癌患者标本中分离和鉴定原发性卵巢癌细胞有助于进一步了解目前临床上使用的微管相互作用剂（MIA）的耐药性的性质。
Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated. All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients’ specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings.
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影响因子：
30.8
作者：
Dumont, P;Leu, JIJ;Murphy, M
通讯作者：
Murphy, M
影响因子：
8.8
作者：
Papadakis, ED;Soulitzis, N;Spandidos, DA
通讯作者：
Spandidos, DA
影响因子：
2.9
作者：
Poruchynsky, MS;Kim, JH;Fojo, T
通讯作者：
Fojo, T
影响因子：
9.7
作者：
Kuroda, Y;Tsukino, H;Katoh, T
通讯作者：
Katoh, T
DOI：
10.1073/pnas.191388598
发表时间：
2001-09-25
影响因子：
11.1
作者：
Gonçalves, A;Braguer, D;Jordan, MA
通讯作者：
Jordan, MA