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Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

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Abstract

Purpose

Ovarian cancer is the leading cause of death among all gynecological malignancies in Western countries. Although therapy for ovarian cancer has been greatly improved in the past 20 years, the overall survival for patients with advanced ovarian cancer has not changed significantly. The poor survival rates in patients with advanced ovarian cancer are due both to late diagnosis and to lack of effective drugs for the majority of patients who have a relapse and develop resistance to current chemotherapy agents used for ovarian cancer. Thus, developing and discovering effective novel drugs with different molecular structures from conventional chemotherapy agents have become an urgent clinical need.

Methods

Ovarian cancer cells were treated with lovastatin and atorvastatin. Apoptosis in these cells and tumor formation in soft agar were determined. The molecular mechanism by which statins suppress ovarian cancer cell growth was evaluated.

Results

Both lovastatin and atorvastatin effectively induced apoptosis in ovarian cancer cells and suppressed anchorage-independent growth of these cells in soft agar. Further investigation of the molecular mechanism has revealed that the expression of Cdc42 and Rac1, small GTPase family members, was highly induced in the cells by these statins along with the activation of Jun N-terminal kinases (JNK). In addition, Bim, a proapoptotic protein, was significantly induced by these statins.

Conclusions

Our findings provide new insight into the molecular mechanism by which statins induce apoptosis in ovarian cancer cells and may lead to novel therapies for advanced ovarian cancer.

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Author information

Authors and Affiliations

  1. The First Affiliated Hospital, Medical College of Xi’an Jiaotong University, 710061, Xi’an, China

    Hongli Liu

  2. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    Shu-Ling Liang

  3. Department of BGES, Cleveland State University, Cleveland, OH, 44115, USA

    Crystal M. Weyman

  4. Department of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA

    Wendy Liu

  5. Clinical Chemistry Program, Department of Chemistry, SI 424, Cleveland State University, Cleveland, OH, 44115, USA

    Hongli Liu, Sheetal Kumar & Aimin Zhou

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  1. Hongli Liu
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  2. Shu-Ling Liang
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  4. Crystal M. Weyman
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  5. Wendy Liu
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Correspondence to Aimin Zhou.

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Liu, H., Liang, SL., Kumar, S. et al. Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression. Cancer Chemother Pharmacol 63, 997–1005 (2009). https://doi.org/10.1007/s00280-008-0830-7

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  • DOI: https://doi.org/10.1007/s00280-008-0830-7

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