Scutellarin inhibits hypoxia-induced epithelial-mesenchymal transition in bladder cancer cells.

Scutellarin, an active component of flavonoid, displays a variety of physiological actions and has been applied for the treatment of diverse diseases including hypertension and cerebral infarction as well as cerebral thrombosis. In recent time, Scutellarin has been demonstrated to possess the anticancer activity. But the biological significance of Scutellarin in bladder cancer (BC) remains to be elucidated. In the current study, we explored the specific effect of Scutellarin on BC progression. We found that Scutellarin inhibited hypoxia-induced BC cell migration and invasion in vitro as well as suppressed hypoxia-induced BC metastasis in vivo. Moreover, Scutellarin significantly reversed hypoxia-promoted epithelial-mesenchymal transition (EMT) in BC cells and the PI3K/Akt and MAPK pathways were implicated in the suppressive effect. Taken together, we suggested the potential value of Scutellarin as a novel anticancer agent for BC treatment.

Glaucocalyxin B protects against oxygen-glucose-deprivation/reperfusion-induced neuronal injury in PC-12 cells.

Oxidative stress has been implicated in the development of cerebral ischemia/reperfusion (I/R) injury. Glaucocalyxin B (GLB), one of five ent-kauranoid diterpenoids, was reported to possess neuroprotective activity. However, the effect of GLB on oxygen-glucose-deprivation/reperfusion (OGD/R)-induced cell injury in PC-12 cells has not been explored. PC-12 cells was treated with various concentrations of GLB (0, 2.5, 5 and 10 µM), and cell viability was detected using the MTT assay. PC-12 cells were pretreated with the indicated concentration of GLB (2.5-10 µM, 2 hours pretreatment), and were maintained under OGD for 3 hours, followed by 24 hours of reoxygenation. Cell viability was assessed using the MTT assay. The levels of superoxide dismutase, malondialdehyde, and glutathione peroxidase were detected using commercially available ELISA Kits. Intracellular reactive oxygen species level was measured using the fluorescent probe 2',7'-dichlorofluorescein diacetate. The levels of Bcl-2, Bax, p-Akt, Akt, p-mTOR, mTOR were detected using Western blot. Our results revealed that GLB significantly protected PC12 cells against OGD/R-induced cell injury. In addition, GLB efficiently inhibited oxidative stress and cell apoptosis in OGD/R-stimulated PC-12 cells. Mechanistic studies revealed that pretreatment with GLB could induce the activation of Akt/mTOR signaling pathway resulting in protection of OGD-treated PC12 cells. In conclusion, our data indicate for the first time that GLB protects against OGD/R-induced neuronal injury in PC-12 cells. The mechanism of the protective effect of GLB is partially associated with activation of the Akt/mTOR signaling pathway. Thus, GLB may be a potential agent for protection against cerebral I/R injury.

Piperlongumine inhibits angiotensin II-induced extracellular matrix expression in cardiac fibroblasts.

Piperlongumine (PL), a single component isolated from Piper longum, has been reported to possess anti-inflammatory, antibacterial, antiangiogenic, antioxidant, antitumor, and antidiabetic activities. However, its role in cardiac fibrosis remains to be clarified. Therefore, we determined the effects of PL on cardiac fibroblasts (CFs) proliferation, and extracellular matrix (ECM) production under angiotensin II (Ang II) conditions, and further investigated the underlying molecular mechanism. Our data revealed that PL inhibited the proliferation and migration of CFs induced by Ang II. In addition, PL blocked the transformation of CFs to myofibroblasts induced by Ang II, as well as decreased cellular reactive oxygen species (ROS) production and malondialdehyde level in Ang II-stimulated CFs. Furthermore, PL significantly suppressed the Ang II-increased phosphorylation of extracellular regulated protein kinase 1/2 (ERK1/2) in CFs. Taken together, the results of the current study demonstrated that PL inhibits Ang II-induced cell proliferation, migration, and ECM expression in CFs through the inactivation of the ERR1/2 signaling pathway. These data strongly suggest that PL may be a promising therapeutic candidate for the treatment of cardiac fibrosis.

Endostar (rh-endostatin) versus placebo in combination with vinorelbine plus cisplatin chemotherapy regimen in treatment of advanced non-small cell lung cancer: A meta-analysis.

BACKGROUND: This meta-analysis was conducted to investigate the efficacy and safety of Endostar (rh-endostatin) versus a placebo in combination with a vinorelbine plus cisplatin (NP) chemotherapy regimen for the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Two reviewers independently searched Medline, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, ASCO, ESMO, the Web of Science, and CNKI databases to locate relevant controlled clinical trials. The treatment efficacy and drug-related toxicity of NP + Endostar (NPE) and NP groups were pooled through meta-analysis according to random or fixed effect models. RESULTS: Fifteen prospective clinical studies were included in this meta-analysis. The pooled risk ratio (RR) for objective response rate was 1.74 (95% confidence interval [CI] 1.43-2.11); the objective response rate in the NPE group was significantly higher than in the NP group (P < 0.05). Nine publications evaluated the incidence of leucopenia between Endostar versus a placebo in combination with an NP chemotherapy regimen. The pooled results showed no statistically significant difference between NPE and NP chemotherapy regimens for leucopenia, thrombocytopenia, and nausea/vomiting risk (P > 0.05). The one-year survival rate in the NPE group was higher than in the NP group, with a statistically significant difference (RR = 1.70, 95% CI 1.07-2.89; P < 0.05). CONCLUSION: Endostar combined with an NP chemotherapy regimen can improve the prognosis of patients with advanced NSCLC without increasing the risk of toxicity.

UCA1 promotes cell proliferation and invasion and inhibits apoptosis through regulation of the miR129-SOX4 pathway in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the most common cancer in kidney malignancies. UCA1 has been identified as an oncogenic lncRNA in multiple cancers, including RCC. However, the underlying molecular mechanism of UCA1 involved in RCC progression is far from being addressed. METHODS: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure expressions of UCA1, miR129, and SOX4 mRNA. Western blot assays were employed to detect SOX4 protein expression. Cell proliferation, invasion, and apoptosis were assessed by CCK-8, Matrigel invasion, and annexin-fluorescein isothiocyanate (FITC) apoptosis-detection assays, respectively. The interaction between UCA1 and miR129 was demonstrated by luciferase, RNA pull-down, and RNA-immunoprecipitation (RIP) assays. Luciferase assays were also used to explore whether UCA1 was able to act as a molecular sponge of miR129 to affect the interplay of miR129 and SOX4. RESULTS: UCA1 expression was upregulated in RCC tissue and cells, and higher UCA1 expression was associated with advanced pathogenic status and poor prognosis of RCC patients. UCA1 knockdown suppressed proliferation and invasion and induced apoptosis in RCC cells. UCA1 inhibited miR129 expression by direct interaction in RCC cells. miR129 overexpression inhibited cell proliferation and invasion and promoted apoptosis. Moreover, miR129 downregulation abrogated UCA1 knockdown-mediated antiproliferation, anti-invasion, and proapoptosis effects in RCC cells. Furthermore, UCA1 acted as a ceRNA of miR129 to enhance target-gene SOX4 expression in RCC cells. CONCLUSION: UCA1 promoted cell proliferation and invasion and inhibited apoptosis by regulating SOX4 via miR129 in RCC, offering a promising therapeutic target and prognosis marker for RCC patients.

LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194.

BACKGROUND: Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported as an oncogene in most malignancies such as lung cancer, esophageal cancer, and gastric cancer. This study is designed to investigate the function of NEAT1 in paclitaxel (PTX) resistance of ovarian cancer and its potential molecular mechanism. PATIENTS AND METHODS: The expressions of NEAT1 and miR-194 in ovarian cancer tissues and cells were estimated by quantitative real-time polymerase chain reaction (qRT-PCR). MTT, flow cytometry, and Western blot assays were used to assess the effect of NEAT1 on PTX resistance in PTX-resistant ovarian cancer cells. Luciferase reporter assay was applied to examine the association between NEAT1, zinc finger E-box-binding homeobox 1 (ZEB1) and miR-194. Xenograft tumor model was established to confirm the biological role of NEAT1 in PTX resistance of ovarian cancer in vivo. RESULTS: NEAT1 was upregulated, and miR-194 was downregulated in PTX-resistant ovarian cancer tissues and cells. Functionally, NEAT1 knockdown enhanced cell sensitivity to PTX via promoting PTX-induced apoptosis in vitro. NEAT1 was identified as a molecular sponge of miR-194 to upregulate ZEB1 expression. Mechanistically, NEAT1-knockdown-induced PTX sensitivity was mediated by miR-194/ZEB1 axis. Moreover, NEAT1 knockdown improved PTX sensitivity of ovarian cancer in vivo. CONCLUSION: NEAT1 contributed to PTX resistance of ovarian cancer cells at least partly through upregulating ZEB1 expression by sponging miR-194, elucidating a novel regulatory pathway of chemoresistance in PTX-resistant ovarian cancer cells and providing a possible long noncoding RNA (lncRNA)-targeted therapy for ovarian cancer.

miRNA-129-5p suppresses cell proliferation and invasion in lung cancer by targeting microspherule protein 1, E-cadherin and vimentin.

Downregulation of microRNA-129 (miR-129) has been described in various types of cancer, however, the significance of miR-129 in lung cancer has not been investigated. The present study, for the first time, determined miR-129-5p expression levels in both lung cancer cell lines and primary lung cancer tissues and also studied the effect of miR-129-5p on the proliferation and invasiveness of lung cancer cells. The results showed that miR-129-5p expression was significantly reduced in both lung cancer cell lines and primary lung cancer tissues (P<0.05). Further research revealed that miR-129-5p could suppress the proliferation and invasion capability of lung cancer cells. Bioinformatics analysis suggested three cancer-related miR-129-5p target genes: Microspherule protein 1 (MCRS1), E-cadherin and vimentin. Further investigation via reverse transcription-quantitative polymerase chain reaction and western blot analysis showed that miR-129-5p was able to reduce the expression levels of MCRS1 and vimentin and enhance the expression of E-cadherin at both the messenger RNA and protein levels. The present results indicate that miR-129-5p is able to suppress lung cancer cell viability and invasion, which may occur via the modulating of MCRS1, E-cadherin and vimentin expression. These findings suggest that miR-129-5p may be a potential biomarker and/or treatment strategy for lung cancer.