Cytotoxicity effect of parthenolide on cancer stem cells in mouse breast cancer stem cells in vivo
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Abstract:
Objective:To investigate the effects of parthenolide (PTL) on cancer stem cells (CSCs) of mouse breast cancer in vivo, providing an experimental basis for the clinical treatment of breast cancer with PTL. Methods: The mouse breast cancer model which enriching for 4T1 breast cancer CSCs was established by chemotherapeutic drug 5-fluorouracil (5-FU). Tumor-bearing mice were randomly divided into three groups, a control group, a 5-FU group and a PTL group. Four weeks later, the mice were sacrificed. The mouse tumor volume and weight were measured. Flow cytometry (FCM) was used to measure the proportion of CD44+CD24-/low cells in different tumor tissues; Hoechst 33342 staining was used to measure the proportion of SP (side population) cells; and the expressions of ALDH1 (aldehyde dehydrogenase1) and CD55 proteins were detected by immunohistochemistry. The formation of mammosphere was observed under an inverted microscope. Results: The mouse breast cancer transplanted model enriching for 4T1 breast cancer CSCs was successfully prepared. PTL could significantly reduce the proportion of CD44+CD24-/low cells in the mouse transplanted tumor tissues (\[42.5±3.7\]% vs \[687±3.2\]%,P<0.05), decrease the percentage of the SP cells in mouse transplanted tumor tissues (\[39.2±18\]% vs \[61.3±2.6\]%,P<0.05), and inhibit the expressions of CD55 and ALDH1 proteins in the mouse tumor tissues (\[18.9±1.5\]% vs \[30.1±1.3\]%,\[8.1±2.3\]% vs \[18.0±1.4\]%; all P<0.05). PTL inhibited the formation of mammosphere generated from the mouse tumor 4T1 cells culturing in serum-free medium and the growth of the mouse transplanted tumor (\[0.625±0.159\]cm3 vs \[1.715±0.184\] cm3, \[1.467±0.373\]g vs \[3.367±0.398\] g; P<0.05\]. Conclusion: PTL can significantly reduce the CSC contents in mouse tumor tissues in vivo, which suggests that PTL could be used to target the breast cancer CSC.
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Project supported by the Natural Science Foundation of Hebei Province (No. H2012206135), and the Science and Technology Research Program of Xingtai City (No. 2012ZC085)