Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model  

作　　者：Li-hua LAI Qi-hong FU Yang LIU Kai JIANG Qing-ming GUO Qing-yun CHEN Bin YAN Qing-qing WANG Jian-gen SHEN 

机构地区：[1]Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China [2]Clinical Medicine College, Hangzhou Normal University, Hangzhou 310036, China [3]Ningbo First Hospital, Ningbo 315000, China

出　　处：《Acta Pharmacologica Sinica》2012年第4期523-530,共8页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by grants from the National Natural Science Foundation of China （30872377）, Education of Zhejiang Province （Y200803762）, Zhejiang Provincial Natural Science Foundation （R2100528）, Ningbo Municipal Bureau of Science and Technology （2010A610058） and also sponsored by Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.

摘　　要：Aim： To investigate the effects of piperine, a major pungent alkaloid present in Piper nigrum and Piper Iongum, on the tumor growth and metastasis of mouse 4T1 mammary carcinoma in vitro and in vivo, and elucidate the underlying mechanisms. Methods： Growth of 4T1 cells was assessed using MTIassay. Apoptosis and cell cycle of 4T1 cells were evaluated with flow cytometry, and the related proteins were examined using Western blotting. Real-time quantitative PCR was applied to detect the expression of matrix metalloproteinases （MMPs）. A highly malignant, spontaneously metastasizing 4T1 mouse mammary carcinoma model was used to evaluate the in vivo antitumor activity. Piperine was injected into tumors every 3 d for 3 times. Results： Piperine （35-280 pmol/L） inhibited the growth of 4T1 cells in time- and dose-dependent manners （the IC5o values were 105±1.08 and 78.52±1.06 pmol/L, respectively, at 48 and 72 h）. Treatment of 4T1 cells with piperine （70-280 pmol/L） dose-dependently induced apoptosis of 4T1 cells, accompanying activation of caspase 3. The cells treated with piperine （140 and 280 pmol/L） significantly increased the percentage of cells in G2/M phase with a reduction in the expression of cyclin BI. Piperine （140 and 280 pmol/L） significantly decreased the expression of MMP-9 and MMP-13, and inhibited 4T1 cell migration in vitro. Injection of piperine （2.5 and 5 mg/kg） dose-dependently suppressed the primary 4T1 tumor growth and injection of piperine （5 mg/kg） significantly inhibited the lung metastasis. Conclusion： These results demonstrated that piperine is an effective antitumor compound in vitro and in vivo, and has the potential to be developed as a new anticancer drug.Aim： To investigate the effects of piperine, a major pungent alkaloid present in Piper nigrum and Piper Iongum, on the tumor growth and metastasis of mouse 4T1 mammary carcinoma in vitro and in vivo, and elucidate the underlying mechanisms. Methods： Growth of 4T1 cells was assessed using MTIassay. Apoptosis and cell cycle of 4T1 cells were evaluated with flow cytometry, and the related proteins were examined using Western blotting. Real-time quantitative PCR was applied to detect the expression of matrix metalloproteinases （MMPs）. A highly malignant, spontaneously metastasizing 4T1 mouse mammary carcinoma model was used to evaluate the in vivo antitumor activity. Piperine was injected into tumors every 3 d for 3 times. Results： Piperine （35-280 pmol/L） inhibited the growth of 4T1 cells in time- and dose-dependent manners （the IC5o values were 105±1.08 and 78.52±1.06 pmol/L, respectively, at 48 and 72 h）. Treatment of 4T1 cells with piperine （70-280 pmol/L） dose-dependently induced apoptosis of 4T1 cells, accompanying activation of caspase 3. The cells treated with piperine （140 and 280 pmol/L） significantly increased the percentage of cells in G2/M phase with a reduction in the expression of cyclin BI. Piperine （140 and 280 pmol/L） significantly decreased the expression of MMP-9 and MMP-13, and inhibited 4T1 cell migration in vitro. Injection of piperine （2.5 and 5 mg/kg） dose-dependently suppressed the primary 4T1 tumor growth and injection of piperine （5 mg/kg） significantly inhibited the lung metastasis. Conclusion： These results demonstrated that piperine is an effective antitumor compound in vitro and in vivo, and has the potential to be developed as a new anticancer drug.

关 键 词：anticancer drug PIPERINE 4T1 breast cancer apoptosis cell cycle METASTASIS MMP-9 MMP-13 

分 类 号：Q26[生物学—细胞生物学] TS264.3[轻工技术与工程—发酵工程]