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Li-Xia Zhong,1 Mo-Li Wu,2 Hong Li,2 Jia Liu,2 Li-Zhu Lin11Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510407, Guangdong, People’s Republic of China; 2Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, People’s Republic of ChinaBackground: Resveratrol (Res) inhibits ovarian cancer (OC) cell growth but its in vivo anti-OC effects are unclear due to the low bioavailability of systemically administered Res. Intraperitoneal administration may overcome this therapeutic dilemma because it makes Res directly affect the abdominal tumors. Ethanol and DMSO are common Res solvents, while their reliability and safety for long-term in vivo treatment remain unknown.Methods: A rat orthotopic OC model was established using the rat NUTU-19 OC cell line. Res dissolved in 10% ethanol or 0.2% DMSO was injected intraperitoneally (20mg/kg/day) into tumor-free and tumor-bearing rats for 2weeks. The tumors were collected for gross, morphological and molecular examinations, and blood and ascitic samples were obtained for a CA125 ELISA. Res concentration in ovarian tissues was determined by high performance liquid chromatography (HPLC).Results: The average tumor weight (0.187±0.065g) of the Res-in-DMSO group was lower than that of untreated (0.426±0.091g; P

// Song Xue 1 , Shu Xiao-Hong 1 , Sha Lin 2 , Bian Jie 2 , Wang Li-Li 1 , Gu Jia-Yao 1 , Shi Shun 1 , Li Pei-Nan 3 , Wu Mo-Li 1 , Wang Qian 1 , Chen Xiao-Yan 1 , Kong Qing-You 1 , Zhang Peng 1 , Li Hong 1 , Liu Jia 1 1 Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China 2 Department of Radiology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China 3 Department of Orthopedics, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China Correspondence to: Hong Li, email: lihongmcn@dlmedu.edu.cn Jia Liu, email: jialiudl@aliyun.com Keywords: resveratrol, orthotopic rat glioblastoma, lumbar puncture, STAT3 signaling, cell death Received: April 07, 2016 Accepted: September 20, 2016 Published: October 3, 2016 ABSTRACT Trans-resveratrol suppresses glioblastoma growth in vitro , but its effects on intracranial glioblastomas remain untested. Resveratrol crosses the blood–brain barrier, and lumbar puncture (LP) greatly increases its bioavailability in rat brains; therefore, we investigated the effectiveness of LP-administered resveratrol on orthotopic rat glioblastomas. Twenty-four tumor-bearing rats were separated into two groups: Group 1 receiving 100 μl saline containing 0.3% DMSO and Group 2 receiving 100 μl resveratrol (300 μM). Treatments started 3 days after transplantation in 2-day intervals until death. Intracranial drug availabilities, tumor sizes, average life spans and the impacts on STAT3 signaling, apoptosis and autophagy rates were evaluated. MRI imaging revealed that average tumor size in the LP group (495.8 ± 22.3 mm 2 ) was smaller than the control groups (810.3 ± 56.4 mm 2 ; P

S100A4 promotes cancer metastasis, but its overall status and splicing manner during gastrocarcinogenesis remains less known. We therefore examined S100A4 frequencies, splicing pattern(s) and the underlying reason(s) for S100A4 expression in gastric cancers. Immunohistochemistry revealed frequent S100A4 expression in intestinal gastric cancers (37/45; 82%) and diffuse gastric cancers (12/20; 60%), but uncommon in noncancerous epithelia (0/12), chronic gastritis (2/24; 8%), and intestinal metaplasia (3/15; 20%). Of 65 primary tumors, 18 were found with focal S100A4 expression, while their LN metastases showed homogenous distribution. S100A4-oriented reverse transcription-polymerase chain reaction yielded a transcript containing exons 1, 3, and 4 (AS1) in 20% of noncancerous, 84% premalignant, and 92% tumor tissues and a transcript harboring exons 1 to 4 (AS2) in 65% of gastric cancers (GCs), 26% premalignant but none in noncancerous tissues. Further analyses found AS1 expression in stromal but not epithelial cells of premalignant tissues, absence of AS2 in endoscopic inflammatory mucosa, and the coexistence of AS1/AS2 in the cultured fibroblasts. Methylation DNA sequencing revealed hypermethylation of four critical CpG sites within S100A4 intron first among S100A4-negative gastric tissues and hypomethylation in S100A4-expressing GC tissues/cell lines. E-cadherin reduction and Wnt activation were common in gastric cancers, which were closely correlated but unnecessarily overlapped with S100A4 expression. Our findings suggest that S100A4 expression is closely related with GC formation, which, as a hypomethylation event, is accompanied with E-cadherin reduction and Wnt activation. The preferential S100A4 AS2 expression in GC cells would have potential values in GC surveillance and prognostic assessment.

In this study, the potential influence of resveratrol (3,5,4'-trihydroxy-trans-stilbene) in signal transducer and activator of transcription 3 (STAT3) signaling of medulloblastoma cells was evaluated by checking the status of STAT3 signaling and its downstream gene expression in two medulloblastoma cell lines (UW228-2 and UW228-3) with and without resveratrol treatment. The results revealed that resveratrol induced neuronal differentiation of medulloblastoma cells. Signal transducer and activator of transcription 3 expression and phosphorylation were detected in normally cultured UW228-2 and UW228-3 cells that were apparently attenuated after resveratrol treatment. The expression of STAT3 downstream genes, survivin, cyclin D1, Cox-2, and c-Myc, was suppressed but Bcl-2 was enhanced by resveratrol. Meanwhile, the production and secretion of leukemia inhibitory factor, a STAT3 activator, became active in resveratrol-treated cells. To further ascertain the significance of STAT3 signaling for medulloblastoma cells, AG490, a selective inhibitor of STAT3 phosphorylation, was used to treat UW228-3 cells. Phosphorylation of STAT3 was inhibited by AG490 accompanied with growth suppression, differentiation-like changes, and down-regulation of survivin, cyclin D1, Cox-2, and c-Myc. Our data thus suggest the importance of STAT3 signaling in maintenance and survival of medulloblastoma cells. This signaling may be the major target of resveratrol. Enhanced leukemia inhibitory factor and Bcl-2 expressions in resveratrol-treated cells might reflect a compensatory response to the loss of STAT3 function.