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Increasing the sensitivity of advanced stage of prostate cancer to chemotherapeutic drugs-induced apoptosis by targeting miR-205 and miR-31.

PURPOSE: Prostate cancer is the major leading cause of death due to cancer amongst men in the United States. There are several chemotherapeutic drugs available for treatment if the cancer is diagnosed at an early (non-malignant) stage. However, there is no treatment available, till date, for the malignant form of cancer. Studies show that Prostate cancer is usually detected when it has reached the malignant stage (1). The purpose of this study is to identify the role of two microRNAs, miR-205 and miR-31, in the regulation of apoptosis in two prostate cancer cell lines. WPE-1 NA22 represents the early stage of prostate cancer and WPE-1 NB26 represents the malignant form (2).

METHODOLOGY: We used microRNA expression analysis to find the microRNAs which are differentially expressed in the two cell lines and the Apoptotic assay to determine their response to various chemotherapeutic drugs. We also did Western blot analysis to see the difference in the protein expression of anti-apoptotic genes in these cell lines.

RESULTS: We have found that WPE-1 NB26 cells express less miR-205 and miR-31 than WPE-1 NA22 cells, and hence have higher levels of anti-apoptotic proteins like Bcl-w and E2F6, respectively. This makes them resistant to the treatment with various apoptotic agents. Also, the Bcl-w and E2F6 stable expressing WPE-1 NA22 cell lines showed high resistance to various chemotherapeutic drugs.

CONCLUSIONS: miR-205 and miR-31 play an important role in apoptosis induced by chemotherapeutic drugs and can be a useful strategy to treat the prostate cancer at an advanced stage.

Namrata Bhatnagar *, Xia Li and Bin Guo

Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND-58105

(1.) Scardino P.T., et al, 1992, Human Pathology, 23, 211-222.

(2.) Webber M.M., et al, 2001, The Prostate, 47:1-13.
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Author:Bhatnagar, Namrata; Li, Xia; Guo, Bin
Publication:Proceedings of the North Dakota Academy of Science
Article Type:Abstract
Geographic Code:1USA
Date:Apr 1, 2009
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