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STAT3 通路对铂类药物的早期反应与上皮性卵巢癌对顺铂的耐药性相关。

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer.

机构信息

The First Affiliated Hospital of Harbin Medical University, Department of Obstetrics and Gynecology, Harbin, China.

出版信息

Braz J Med Biol Res. 2013 Aug;46(8):650-8. doi: 10.1590/1414-431X20133003. Epub 2013 Aug 13.

DOI:10.1590/1414-431X20133003
PMID:23969971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3854422/
Abstract

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

摘要

顺铂耐药仍然是治疗上皮性卵巢癌的主要障碍之一。由于奥沙利铂和奈达铂在临床试验中对顺铂耐药的卵巢癌有效，并且信号转导子和转录激活子 3（STAT3）与顺铂耐药相关，我们研究了奥沙利铂和奈达铂是否通过 STAT3 通路克服顺铂耐药与卵巢癌有关。我们使用 Alamar blue、集落形成和划痕愈合测定以及 Western blot 分析来比较铂类药物在 SKOV-3 细胞中的作用。在等毒性剂量下，奥沙利铂和奈达铂对集落形成能力的抑制作用与顺铂相似，对卵巢癌细胞迁移的抑制作用大于顺铂。在药物给药的早期，顺铂增加了 pSTAT3（Tyr705）、STAT3α、VEGF、存活素和 Bcl-XL 的表达，而奥沙利铂和奈达铂则表现出相反的作用，上调了 pSTAT3（Ser727）和 STAT3β。STAT3 通路对与上皮性卵巢癌顺铂耐药相关的铂类药物反应迅速，为逆转顺铂耐药提供了新的治疗策略的依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/54556cfc675f/1414-431X-bjmbr-46-08-0650-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/d22e39b7bdf2/1414-431X-bjmbr-46-08-0650-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/5c51c328dc43/1414-431X-bjmbr-46-08-0650-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/45e83e05c111/1414-431X-bjmbr-46-08-0650-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/7deb371906b4/1414-431X-bjmbr-46-08-0650-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/54556cfc675f/1414-431X-bjmbr-46-08-0650-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/d22e39b7bdf2/1414-431X-bjmbr-46-08-0650-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/5c51c328dc43/1414-431X-bjmbr-46-08-0650-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/45e83e05c111/1414-431X-bjmbr-46-08-0650-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/7deb371906b4/1414-431X-bjmbr-46-08-0650-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/3854422/54556cfc675f/1414-431X-bjmbr-46-08-0650-gf05.jpg

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