4.6 Article

Musashi-2 is a novel regulator of paclitaxel sensitivity in ovarian cancer cells

期刊

INTERNATIONAL JOURNAL OF ONCOLOGY
卷 49, 期 5, 页码 1945-1952

出版社

SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3683

关键词

Musashi-2; paclitaxel; drug resistance; ovarian cancer cells; apoptosis; cytotoxicity

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资金

  1. Konkuk University
  2. National Research Foundation of Korea (NRF) from the Ministry of Science, ICT and Future Planning [2013R1A1A1012205, 20110028646]
  3. National Research Foundation of Korea [2013R1A1A1012205] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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As few prognostic markers and symptoms have been identified, ovarian cancer is typically diagnosed at an advanced stage, and a majority of patients will relapse and develop resistance to anticancer drugs such as paclitaxel. Musashi-2 (MSI2) is a regulator of gene translation and functions as an oncogenic protein and a marker of poor prognosis in various types of cancer. However, the biological and clinical significance of MSI2 in ovarian cancer remains unclear. Using a tissue microarray-based assay, we demonstrated that MSI2 was highly expressed in advanced, serous ovarian cancer tissues. In addition, MSI2-overexpressing ovarian cancer cells exhibited increased viability, proliferation and growth. We found that MSI2 was overexpressed in paclitaxel-resistant ovarian cancer SKOV3-TR cells but not in paclitaxel-sensitive cell lines. The loss of MSI2 expression in lentivirus-mediated stable MSI2 knockdown SKOV3-TR cells impaired paclitaxel resistance as determined using cell viability and apoptosis assays. In contrast, lentivirus-mediated MSI2 overexpression promoted the development of paclitaxel resistance in paclitaxel-sensitive ovarian cancer cells. The results of the present study are the first to demonstrate that MSI2 is a valuable marker of advanced, serous ovarian cancer and that MSI2 plays an important role in paclitaxel resistance.

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