目的: 调查胡椒碱,在 Piper nigrum 在场的主要的刺鼻的碱和 Piper longum 的效果,在肿瘤生长和老鼠 4T1 的转移上在 vitro 并且在 vivo 的乳房的癌,并且阐明内在的机制。
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.