Honglei Jiang

Capsaicin Mediates Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells via Stabilizing and Activating p53

Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicins antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicins antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.

MicroRNA-195 regulates steroid receptor coactivator-3 protein expression in hepatocellular carcinoma cells

Multiple studies have shown that steroid receptor coactivator-3 (SRC-3) is upregulated and promotes cell proliferation in several human cancers, including breast, lung, and prostate carcinoma. However, its molecular determinants remain largely unexplored. In the current study, by way of informatics software, we found that MicroRNA-195 (miR-195) could negatively regulate protein levels of SRC-3 through targeting its 3′-untranslated region (3′-UTR) in hepatocellular carcinoma (HCC) cells. As a result, miR-195 mimics inhibited while its antisense enhanced SRC-3 protein levels. Furthermore, miR-195 could modulate cell proliferation and tumor growth in vivo and in vitro. Therefore, our results demonstrate a novel molecular mechanism for the dysregulated expression of SRC-3 in hepatocellular carcinoma.

Transcription Factor MafB Promotes Hepatocellular Carcinoma Cell Proliferation through Up-Regulation of Cyclin D1

Background/Aims: MafB, a member of the Maf transcription factor family, plays a key role in the regulation of pancreatic alpha and beta cell differentiation. However, its function in the control of cancer cell proliferation remains unknown. Methods: The mRNA and protein expression levels of MafB in hepatocellular carcinoma tissues and adjacent non-tumor normal specimens were determined by real-time RT-PCR and Western blot, respectively. Report assay was performed to determine whether the regulation of Cyclin D1 by MafB is at the transcriptional level. The binding of MafB to the Cyclin D1 promoter was determined by Chromatin Immunoprecipitation (ChIP) assays. To determine the potential oncogenic effects of MafB in vivo, HepG2 cells transfected with adenovirus containing empty vector or MafB were injected subcutaneously to the skin under the front legs of the nude mice. Results: In the current study, we showed that MafB was markedly up-regulated in hepatocellular carcinoma (HCC) tissues and cells. Enforced overexpression of MafB enhanced, while its deficiency inhibited HCC cell proliferation. Mechanistically, Cyclin D1, an important regulator of cell cycle progression, was identified as a direct transcriptional target of MafB. Consistently, knockdown of Cyclin D1 largely attenuated the proliferative roles of MafB in HCC cells. Importantly, MafB overexpression significantly promoted cancer cell growth in mice. Conclusions: Collectively, our results identified a novel HCC regulatory pathway involving MafB and Cyclin D1, the dysfunction of which drives proliferative character in HCC.

Expression of CXCR6 on CD8+ T cells was up-regulated in allograft rejection

CXCL16/SR-PSOX is a novel transmembrane-type chemokine, which was also identified as a novel scavenger receptor for oxidized low density lipoprotein. Its receptor CXCR6 expresses on activated CD8(+) T cells, type 1-polarized CD4(+), and constitutively expresses on NKT cells. Moreover, it has been shown that CXCL16 accumulated activated CD8(+) T cells to sites of inflammation. To date, the effect of CXCL16 (SR-PSOX)/CXCR6 on CD8(+) T cells and its role in allograft rejection/acceptance are not well understood. In the current study, we show that rejected allografts showed higher expressions of CXCR6 and CXCL16. More importantly, expression of CXCR6 on CD8(+) T cells was also up-regulated by rejection. However, the blockade of CXCL16(SR-PSOX)/CXCR6 interaction could not inhibit cytotoxic activity of CD8(+) T cells, and therefore, could not prolong the cardiac graft survival time.

DAX-1 Inhibits Hepatocellular Carcinoma Proliferation by Inhibiting β-Catenin Transcriptional Activity

Background/Aims: Hepatocellular carcinoma (HCC) represents the most common type of liver cancer. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1), an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains, has been known for its fundamental roles in the development, especially in the sex determination and steroidogenesis. Previous studies also showed that DAX-1 played a critical role in endocrine and sex steroid-dependent neoplasms such as adrenocortical, pituitary, endometrial, and ovarian tumors. However, its biological roles in the development of HCC remain largely unexplored. Methods: Real-time PCR and Western blot were used to detect the expression of DAX-1 in HCC tissues and cell lines. Immunoprecipitation (IP) assay was used to show the interaction between DAX-1 and β-Catenin. Small interfering RNA (siRNA) was used to silence the expression of DAX-1. BrdU incorporation and Cell-cycle assays were used to detect the role of DAX-1 in HCC cells proliferation. Migration and invasion assays were carried out to test the metastasis ability of DAX-1 in HCC cells. Results: In the present study, we found that mRNA and protein levels of DAX-1 were down-regulated in HCC tissues and cell lines. Furthermore, overexpression of DAX-1 could inhibit while its knockdown using small interfering RNA promoted cell proliferation in several HCC cell lines. At the molecular level, we demonstrated that DAX-1 could interact with β-Catenin and attenuate its transcriptional activity. Conclusion: Therefore, our results suggest a previously unknown DAX-1/β-Catenin molecular network controlling HCC development.

Efficacy of fast track surgery in laparoscopic radical gastrectomy for gastric cancer:a meta-analysis of randomized controlled trials

OBJECTIVE To conduct a systematic review of efficacy and security of fast track surgery (FTS) in laparoscopic radical gastrectomy for gastric cancer. METHODS We searched PubMed, Embase, and Cochrane Library Databases and supplemented by other searches to collect randomized controlled trials (RCTs) on the comparison of fast track surgery combined with laparoscopy versus laparoscopy separately used in radical gastrectomy for gastric cancer before December 2016. After screening for inclusion, data extraction, and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. RESULTS A total of 6 RCTs, involving 464 patients, were included. There were 232 patients in the FTS group and conventional care group separately. Compared with the conventional care group, patients of FTS group had shorter postoperative hospital stay [WMD = -1.85, 95%CI: (-2.60, -1.11), P < .00001], earlier first flatus [WMD = -9.33, 95%CI: (-13.74, -4.91), P < .0001], lower level of C-reactive protein (CRP) at postoperative day 4 [WMD = -13.94, 95%CI: (-22.74, -5.15), P = .002], and less hospitalization fees [SMD = -1.12, 95%CI: (-2.07, -0.18), P = .02]. There were no significant differences in operation time, intraoperative blood loss, and postoperative complications between the two groups. CONCLUSION Based on current evidence, the FTS protocol is safe and effective in laparoscopic radical gastrectomy for gastric cancer. Due to the limitations of our study, further larger and multicenter studies are needed to validate our findings.

Eupafolin Exhibits Potent Anti-Angiogenic and Antitumor Activity in Hepatocellular Carcinoma

Eupafolin is a flavonoid extracted from the common sage herb which has been used in China as traditional medicine. Previous studies had reported that eupafolin had antioxidative, anti-inflammatory and antitumor effects. However, the function and the mechanism of eupafolin to exert its antitumor activity, especially its effect on tumor angiogenesis, have not been elucidated. Herein, we showed that eupafolin significantly inhibited vascular endothelial growth factor (VEGF)-induced cell proliferation, migration and tube formation of human umbilical vascular endothelial cells (HUVECs) in a dose-dependent manner. Meanwhile, the new blood microvessels induced by VEGF in the matrigel plug were also substantially suppressed by eupafolin. The results of HCC xenograft experiments demonstrated eupafolin remarkably inhibited tumor growth and tumor angiogenesis in vivo, suggesting the antitumor activity exerted by eupafolin was closely correlated with its potency on tumor angiogenesis. Mechanism investigations revealed that eupafolin significantly blocked VEGF-induced activation of VEGFR2 in HUVEC cells as well as its downstream signaling pathway. In addition to the effect on endothelial cells, through inhibiting Akt activity in tumor cells, VEGF secretion in HepG2 was dramatically decreased after eupafolin treatment. Our study was the first to report the activity of eupafolin against tumor angiogenesis as well as the underlying mechanism by which eupafolin to exert its anti-angiogenic activity.