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

AIM: To investigate the effects of piperine, a major pungent alkaloid present in Piper nigrum and Piper longum, 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 MTT assay. 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 µmol/L) inhibited the growth of 4T1 cells in time- and dose-dependent manners (the IC(50) values were 105 ± 1.08 and 78.52 ± 1.06 µmol/L, respectively, at 48 and 72 h). Treatment of 4T1 cells with piperine (70-280 µmol/L) dose-dependently induced apoptosis of 4T1 cells, accompanying activation of caspase 3. The cells treated with piperine (140 and 280 µmol/L) significantly increased the percentage of cells in G(2)/M phase with a reduction in the expression of cyclin B1. Piperine (140 and 280 µmol/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.

[Antiangiogenesis effect of linomide in treatment of transplanted human oral carcinoma in nude mice and its relations to regulation on cytokine secretion of macrophage]

OBJECTIVE: To investigate the antiangiogenesis effect of linomide in treatment of transplanted human squamous cell carcinoma of tongue in BALB/C nude mice and to study its relations to regulation on cytokine secretion of macrophages. METHODS: An animal model was established by inoculating the human squamous cell carcinoma cell line Tca8113 into the BALB/c nu/nu nude mice. The mice were randomly divided into three groups and received linomide therapy. The microvessel density (MVD) in the tumor tissue was investigated by immunohistochemistry The productions of TNFalphaand GM-CSF of peritoneal macrophages derived from the tumor -bearing nude mice and cultured murine macrophage cell line RAW264.7 after linomide treatment were detected by ELISA assay. RESULTS: It showed that the tumor weight of mice injected intraperitoneally with 100 mg/kg d-(1), 50 mg/kg d-(1) linomide and mice of control group were 0.47+/-0.25g, 0.92+/-0.30g and 1.75+/-0.38g, respectively. The microvessel density (MVD) in tumor tissue from mice treated with linomide 100 mg/kg d-(1), 50 mg/kg d-(1) decreased 38.2%, 57.8% respectively when compared with that in mice of control group. After linomide treatment, the function of TNFalpha secretion of peritoneal macrophages from tumor-bearing nude mice was significantly inhibi ted when compared with macrophages from untreated mice. And linomide inhibited the release of TNFalpha of RAW264.7 cells in a dose dependent manner. CONCLUSION: It indicats that linomide can effectively inhibit the growth of human squamous carcinoma of tongue in nude mice and decrease the microvessel density in the tumor tissue. The affection of release of antiangiogenic factor TNFalpha of macrophage may be an important mechanism of antitumor activity of linomide.

[The use of self-reinforced P(L/D)LA bioabsorbable internal fixation system in oral maxillofacial fractures].

PURPOSE: The purpose of this study was to evaluate the effectiveness of self-reinforced P(L/D)LA internal fixation system for oral maxillofacial fractures. METHODS: The system was used in 43 patients. The reduction situation during and after operation, postoperative complications and degradation time were recorded. RESULTS: The postoperative complications were one case with postoperative infection and one case with late noninfectious inflammatory tissue response, but these were controlled by routine treatment. Bone healing was satisfactory in all cases, without delay of bone union or obvious displacement of fracture segments after surgery. The degradation time ranged from one and half years to three years, the system remained in orbital and zygomatic areas and cannot be degraded completely. CONCLUSIONS: The SR-P(L/D)LA system provided effective and stable fixation for maxillofacial fractures. The system has some defaults: the screws are broken easily, different degradation time in different individuals and incomplete degradation in some patients exist.

[Oral-facial-digits syndrome I: case report].

To report a case of oral-facial-digits syndrome I who underwent plastic surgery of tongue, palate and digital abnormalities. The tongue of the patient restored normal mobility approximately but the speech function could not recover completely. The function recovery of the patient depended on the degree of mental retardation, its possible mechanism was the mutation of OFD I gene.