Black rice-derived anthocyanins inhibit HER-2-positive breast cancer epithelial-mesenchymal transition-mediated metastasis in vitro by suppressing FAK signaling.

This study aimed to investigate the role of focal adhesion kinase (FAK) signaling in the inhibitory effects of black rice anthocyanins (BRACs) on human epidermal growth factor receptor-2 (HER-2)-positive human breast cancer cell metastasis, using the MCF-10A, MCF-7 and MDA-MB-453 cells. BRACs exerted an anti-metastatic effect on the HER-2-positive breast cancer cells. The effects of BRACs on the proliferation of the MDA-MB-453 cells were examined by cell counting kit-8 assay. A wound-healing assay was used to examine the effects of BRACs on the migration of the breast cancer cells. BRACs interrupted migration and invasion. BRACs decreased the migration distance of the HER-2-positive human breast cancer cells, MDA-MB-453, by 37% compared with the cells in the untreated group. They also reduced the number of invading MDA-MB-453 cells by 68%. In addition, BRACs exerted an inhibitory effect on epithelial-mesenchymal transition. Western blot analysis revealed that BRACs decreased the phosphorylation of FAK, cSrc and p130Cas. The FAK inhibitor, Y15, was also used to further evaluate the role of FAK signaling in the anti-metastatic effects of BRACs on MDA-MB-453 cells. The results of western blot analysis revealed that BRACs increased the expression of the epithelial marker, E-cadherin, and decreased the expression of the mesenchymal markers, fibronectin and vimentin, in the MDA-MB­453 cells. In addition, BRACs decreased the interaction between HER-2 and FAK, FAK and cSrc, cSrc and p130Cas, and between FAK and p130Cas. These results suggest that BRACs suppress the metastasis of HER-2-positive breast cancer in vitro, and that the cSrc/FAK/p130Cas pathway plays a vital role in this inhibitory effect.

[The Effects of All-trans Retinoic Acid on the Expression of Inflammatory Cytokines and Cartilage Damage Related Protease in Rats with Collagen Induced Arthritis].

OBJECTIVES: To investigate the effects of all-trans retinoic acid (ATRA) on arthritis and the expressions of inflammatory cytokines and cartilage damage related proteases of the collagen-induced arthritis model (CIA) rats in vivo. METHODS: The CIA model of rheumatoid arthritis was induced with C2 and incomplete Freund's adjuvant. The rats were randomly divided into control group, CIA model group and two ATRA dose groups (ATRA 0.50 mg/kg group and ATRA 1.00 mg/kg group). ATRA were given three times per week for six weeks in ATRA groups. Morphological changes, arthritis index (AI) scores, the semi-quantitative scores of pathology damage, the protein expressions of cartilage damage related proteases and the serum levels of TNF-α, IL-17A, IFN-γ, IL-4, IL-10 were observed. RESULTS: The AI scores of ATRA groups were similar to CIA model group ( P<0.05). Apparent morphological disorders in knee and ankle joints were observed in the CIA model group and ATRA 1.00 mg/kg group. The structure of knee joint was improved slightly in ATRA 0.50 mg/kg group. The serum levels of TNF-α, IFN-γ and IL-17A were decreased in both ATRA groups; ATRA also can increase the serum level of IL-4. Compared to CIA model group, the protein expressions of ADAMTS-4, MMP3, MMP1 were decreased in both ATRA groups ( P<0.05). CONCLUSIONS: ATRA, which was able to inhibit pro-inflammatory cytokines secretion, could correct the imbalance of Th1/Th2 and Th17/Treg. ATRA also can reduce the expressions of cartilage damage related proteases, which proved that ATRA may have a beneficial effect on rheumatoid arthritis.

[Effects of the Chinese patent medicine, Honghua Injection, on platelet glycoprotein IIb/III a receptors in patients with acute coronary syndrome: a randomized controlled trial].

BACKGROUND: Glycoprotein (GP) IIb/IIIa is an important index for assessing the function of platelets. To investigate the effects of Honghua Injection, a Chinese patent medicine made from extracts of Carthamus tinctorius L, on GP IIb/IIIa is a key study in evaluating the inhibition properties of Honghua Injection on platelet aggregation. OBJECTIVE: To observe the effects of Honghua Injection on platelet GPIIb/IIIa receptors and explore the mechanisms of Honghua Injection in inhibiting platelet aggregation in patients with acute coronary syndrome. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 64 patients from Yueyang Hospital of Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine were randomly divided into Honghua Injection group (n=32, routine Western medicine plus Honghua Injection) and control group (n=32, routine Western medicine) according to the random number table. The patients were treated for 14 d. MAIN OUTCOME MEASURES: The expressions of GPIIb/IIIa (CD41), P-selection (CD62p), and lysosome-associated membrane GP (CD63) were measured by flow cytometry before and after treatment. Meanwhile the therapeutic effects of Huonghua Injection on angina and short-term prognosis were observed. RESULTS: The observational period was 14 d and four patients in the control group were omitted due to early discharge. The expression of CD41 in both the Honghua Injection group and the control group was inhibited after treatment (P<0.05, P<0.01). The inhibition of the Honghua Injection group was stronger than that of the control group (P<0.05). There was no case of death, myocardial infarction and cerebral apoplexy during 14 d of treatment. The improvement of angina symptoms and electrocardiographic manifestation in the Honghua Injection group was greater than that of the control group (P<0.05). CONCLUSION: Honghua Injection can inhibit the expression of GP IIb/IIIa receptors by preventing aggregation of platelets and may be considered as an effective traditional Chinese medicine for acute coronary syndrome.