Erratum.

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo. In our study, we found that emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin and decreasing the expression of N-cadherin, Snail, and -catenin. Emodin also significantly inhibited the activation of the Wnt/-catenin signaling pathway by downregulating the expression of related downstream target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/-catenin signaling pathway agonist abolished the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the Wnt/-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition of the Wnt/-catenin signaling pathway.

Emodin Inhibits Colon Cancer Cell Invasion and Migration by Suppressing Epithelial-Mesenchymal Transition via the Wnt/ß-Catenin Pathway.

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo. In our study, we found that emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin and decreasing the expression of N-cadherin, Snail, and ß-catenin. Emodin also significantly inhibited the activation of the Wnt/ß-catenin signaling pathway by downregulating the expression of related downstream target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/ß-catenin signaling pathway agonist abolished the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the Wnt/ß-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/ß-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition of the Wnt/ß-catenin signaling pathway.

Effects of lignans extracted from Eucommia ulmoides and aldose reductase inhibitor epalrestat on hypertensive vascular remodeling.

AIM OF THE STUDY: To investigate the effects of lignans extracted from Eucommia ulmoides and epalrestat on vascular remodeling in spontaneously hypertensive rats. MATERIALS AND METHODS: Ten-week-old male spontaneously hypertensive rats were randomly divided into 3 groups (12 rats each group), and treated orally with 100 mg/kg/d of captopril (an angiotensin-converting enzyme inhibitor), 100 mg/kg/d of epalrestat (an aldose reductase inhibitor) and 300 mg/kg/d of lignans by gavage daily for 16 weeks, respectively. Sex-, age-, and number-matched spontaneously hypertensive rats and normotensive Wistar Kyoto rats, were treated with distilled water (vehicle) as controls. The rats were weighed weekly. Mean arterial blood pressure and heart rate were measured periodically by non-invasive blood pressure monitoring. They were sacrificed at the end of experiment (26-week-old). Superior mesenteric artery and aorta were isolated for determination of histomorphometry and the expression of aldose reductase by immunohistochemistry. RESULTS: Captopril and lignans, but not epalrestat, decreased mean arterial blood pressure in spontaneously hypertensive rats. Vascular remodeling was improved in all three treated groups by histomorphometry. CONCLUSIONS: Both lignans and epalrestat reversed hypertensive vascular remodeling. Aldose reductase played a vital role in the pathologic process of hypertensive vascular remodeling rather than elevation of blood pressure. These data suggested that aldose reductase could be a new therapeutic target for the treatment of cardiovascular diseases.

[Clinicopathological significance of microRNA-21 and miR-125 expression in colorectal cancer].

OBJECTIVE: To investigate the expression of microRNA(miR)-21 and miR-125 in colorectal cancer (CRC) and its relationship with clinicopathological features. METHODS: Quantitative real-time PCR was applied to examine the expression of miR-21 and miR-125 in 100 primary CRC specimens which were diagnosed and operated in West China Hospital between 2006 and 2007, in comparison with the corresponding normal mucosa specimens. The relationship between the expression of miRNAs and clinicopathological features was analyzed. RESULTS: The expression of miR-21 in CRC was up-regulated by 2.3 times compared to normal mucosa (P =0.025), while the expression of miR-125 was down-regulated by 3.3 times in comparison with normal mucosa (P =0.005). Furthermore, the expression of miR-21 was related to TNM stage (P =0.028) and local invasion (P =0.023). On the other hand, no significant relationship was found between the expression of miR-125 and clinicopathological features (P >0.05). CONCLUSION: The over-expression of miR-21 may play a role in the development and progression of CRC, while miR-125 may not be related to the pathogenesis of CRC.

[Genotyping of AKAP10 gene 2073A/G single nucleotide polymorphism by TaqMan probe real-time PCR].

OBJECTIVE: To detect AKAP10 gene 2073A/G single nucleotide polymorphism (SNP) genotyping by TaqMan probe real-time PCR. METHODS: The genotype of AKAP10 gene 2073A/G was detected by real-time PCR with a pair of new-designed TaqMan probes. The PCR products also were subjected to gene sequence analysis to validate the results of TaqMan probe real-time PCR. RESULTS: The TaqMan probe real-time PCR method was successfully developed to detect AKAP10 gene 2073A/G SNP. The results were accordant with those achieved by DNA sequencing. The distribution of AKAP10 gene 2073A/G among population had no relationship with gender, age (P > 0.05). Unconditional logistic regression analysis revealed that the variant genotypes (AG + GG) had a 52% increased risk of colorectal cancer, compared with the AA genotype (P = 0.019). CONCLUSION: A detection platform for SNP genotyping by TaqMan probe was set up successfully. There was a significant association between AKAP10 gene 2073A/G and colorectal cancer.

The Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 and the risk of colorectal cancer.

OBJECTIVE: The purpose of this study is to investigate whether the Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) is related to the risk of colorectal cancer (CRC), clinicopathological variables and the environmental factors for the development of CRC. METHODS: Applying TaqMan allelic discrimination, we investigated AKAP10 Ile646Val (2073A>G) polymorphism in 288 Chinese CRC patients and 281 healthy controls. RESULTS: Logistic regression analysis revealed a significant association of AKAP10 Ile646Val (2073A>G) polymorphism with increased CRC risk (adjusted OR = 1.44, 95% CI 1.01-2.07, p = 0.02). Stratification analysis showed that the increased risk associated with the variant genotypes (GG+AG) was more evident in male subjects (adjusted OR = 1.48, 95% CI 0.94-2.34, p = 0.03). Compared with the AA genotype, the adjusted OR for the variant genotypes was 1.81 (95% CI 1.08-3.05, p = 0.01) among young subjects (age <57 years). Among individuals who did not smoke or who smoked lightly, there was a significantly increased risk with the variant genotypes (adjusted OR = 1.66, 95% CI 1.08-2.56, p = 0.02). We did not observe a relationship between the AKAP10 polymorphism and other clinicopathological and environmental factors. CONCLUSIONS: Our data suggested that the AKAP10 2073A>G variation is associated with an increased risk of CRC in the Chinese population.