共查询到20条相似文献,搜索用时 46 毫秒
1.
Wang W Li X Sun W Zhang L Zhang M Hong B Lv G 《Journal of cancer research and clinical oncology》2012,138(9):1597-1605
Purpose
Triptolide (TPL) is a diterpenoid triepoxide that effectively induces apoptosis in a wide variety of cancer cells. However, the detailed mechanism by which TPL activates caspase cascade remains elusive. This study aimed to examine the antitumor effects of TPL against pancreatic cancer and investigate the underlying mechanism.Methods
Cell proliferation was evaluated by sulforhodamine B assay. The apoptosis was evaluated by caspase activity assay, Western blot and flow cytometry. DcR3 level was measured by ELISA. AsPC-1 xenografts were established to compare the in vivo antitumor effects of TPL and Gemcitabine.Results
TPL inhibited the proliferation and induced the apoptosis of pancreatic cancer cells in a dose- and time-dependent manner. TPL also inhibited DcR3 expression in a dose- and time-dependent manner. siRNA-mediated DcR3 knockdown sensitized pancreatic cancer cells to TPL-induced apoptosis. In vivo, DcR3 siRNA significantly enhanced TPL-induced apoptosis and tumor growth inhibition. Moreover, TPL showed less toxicity compared to Gemcitabine in mice model.Conclusions
TPL induces the apoptosis of pancreatic cancer cells via the downregulation of DcR3 expression and has the potential as an effective agent against pancreatic cancer. 相似文献2.
Xiaodong Tian Kun Hao Changfu Qin Kun Xie Xuehai Xie Yinmo Yang 《Digestive diseases and sciences》2013,58(9):2705-2712
Background
Insulin-like growth factor 1 receptor (IGF1R) plays important roles in the progression of pancreatic cancer. However, the underlying mechanism remains unclear.Aims
The purpose of this study was to investigate the effects of IGF1R knockdown on the proliferation, apoptosis and chemosensitivity of pancreatic cancer cells, and explore the possible mechanisms.Methods
Pancreatic cancer cells expressing IGF1R shRNA were established, and the cell proliferation, colony formation, and chemosensitivity to gemcitabine were examined in vitro. The activation of AKT and NF-κB was detected by Western blot analysis and luciferase assay, respectively. Xenograft mice models were established to evaluate the in vivo anti-tumor effects of IGF1R knockdown.Results
IGF1R knockdown notably inhibited pancreatic cancer cell proliferation and colony formation, induced apoptosis, and inhibited xenograft tumor growth. Moreover, IGF1R knockdown significantly enhanced chemosensitivity to gemcitabine in pancreatic cancer cells, and this was correlated with the inhibition of PI3K/AKT and NF-κB pathways.Conclusions
IGF1R knockdown suppresses tumor growth and enhances chemosensitivity in pancreatic cancer via the inhibition of PI3K/AKT and NF-κB pathways, and is a promising approach to overcome the chemoresistance of pancreatic cancer. 相似文献3.
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Jun Yamao Hideyoshi Toyokawa Songtae Kim So Yamaki Sohei Satoi Hiroaki Yanagimoto Tomohisa Yamamoto Satoshi Hirooka Yoichi Matsui A-Hon Kwon 《Journal of hepato-biliary-pancreatic sciences》2013,20(2):206-213
Background
To investigate the behavior of activated pancreatic stellate cells (PSCs), which express alpha-smooth muscle actin (α-SMA), and pancreatic cancer cells in vivo, we examined the expression of α-SMA-positive myofibroblast-like cells in pancreatic cancer tissue after treatment with gemcitabine (GEM) using a Lewis orthotopic rat pancreatic cancer model.Methods
The effect of GEM on DSL-6A/C1 cell proliferation was determined by cell counting method. The orthotopic pancreatic cancer animals were prepared with DSL-6A/C cells, and treated with GEM (100 mg/kg/weekly, for 3 weeks). At the end of treatment, α-SMA expression, fibrosis, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) were evaluated by histopathological and Western blot analyses.Results
DSL-6A/C1 cell proliferation was significantly reduced by co-culturing with GEM in vitro. Survival time of pancreatic cancer animals (59.6 ± 13.4 days) was significantly improved by treatment with GEM (89.6 ± 21.8 days; p = 0.0005). Alpha-SMA expression in pancreatic cancer tissue was significantly reduced after treatment with GEM (p = 0.03), however, there was no significant difference in Sirius-red expression. Expression of VEGF was significantly reduced by GEM treatment, but the expression of TGF-β1 was not inhibited.Conclusion
GEM may suppress not only the tumor cell proliferation but also suppress PSCs activation through VEGF reduction. 相似文献8.
Chen Y Kang M Lu W Guo Q Zhang B Xie Q Wu Y 《Journal of cancer research and clinical oncology》2012,138(9):1463-1474
Purpose
Aberrant expression of DJ-1 has been proven to be associated with tumorigenesis in many carcinomas. However, its role in pancreatic cancer is unknown. The aims of this study were to investigate whether the serum DJ-1 might be a potential biomarker for pancreatic cancer and to determine the biologic function of DJ-1 expression in gemcitabine-induced chemoresistance of pancreatic cancer.Methods
The serum level of DJ-1 was higher in 128 pancreatic cancer patients compared with 62 healthy controls by ELISA. To determine the effect of DJ-1 on pancreatic tumor chemoresistance, a siRNA-targeting DJ-1 was synthesized and a stably transfected cell line with DJ-1 over-expression was constructed. The mechanism of tumor chemoresistance was assessed by multiple methods, such as MTT assay, real-time PCR, Western blot and flow cytometry.Results
The serum level of DJ-1 was higher in pancreatic cancer patients than healthy controls, and it has the relationship with tumor differentiation in pancreatic cancer. Down-regulation of DJ-1 enhanced gemcitabine-induced apoptosis in three pancreatic cancer cell lines. On the contrary, over-expression of DJ-1 desensitized the MIA PaCa-2 to the induction of apoptosis by gemcitabine.Conclusions
Our results suggest that the serum level of DJ-1 may be a potential biomarker for pancreatic cancer, and that DJ-1 plays critical roles in the pancreatic tumor chemoresistance, supporting the development of chemotherapeutic approaches targeting this oncogene. 相似文献9.
Liu Y Yan X Liu N Zhou J Liu J Pang H Cao J Liu Y Wang Y Liu L Zhang H 《Journal of cancer research and clinical oncology》2012,138(8):1329-1338
Purpose
To explore the relationship between the expression of ZEB1 gene and the proliferation ability of lung adenocarcinoma cells.Methods
Immunohistochemistry, Western blot and Real-time PCR were used to detect the expression of ZEB1 gene in lung adenocarcinoma tissue and cell lines compared with adjacent noncancerous region and the human lung fibroblast cell HLF cells. The lentivirus RNA interference technique was used to knock down the expression of ZEB1 in lung adenocarcinoma A549 and H1299 cell lines. Cell cycle and cell apoptosis were measured by FCM assay. In vivo, four groups of 4-week-old nude mice were subcutaneously injected with the stably transfected (ZEB-si, scr-si) cells at a single site to investigate the effect of ZEB1-siRNA in the nude mice tumor growth. In situ apoptosis was detection by TUNEL assay.Results
ZEB-1 was highly expressed in lung adenocarcinoma tissue and cell lines compared with adjacent noncancerous region and the human lung fibroblast cell HLF cells. ZEB1-siRNA could decrease lung adenocarcinoma cell proliferation by delaying S-phase entry and induce cell apoptosis, which led to the inhibition of the tumorigenicity of A549 and H1299 cell lines. Further investigation showed that injecting the ZEB1-siRNA cells into the nude mice could significantly decrease the tumor growth.Conclusion
Knockdown of ZEB-1 expression by lentivirus-delivered siRNA may provide a novel therapeutic target for the treatment of lung cancer. 相似文献10.
Motohiko Kato Kenji Watabe Masahiko Tsujii Tohru Funahashi Iichiro Shimomura Tetsuo Takehara 《Digestive diseases and sciences》2014,59(6):1192-1196
Background
Adiponectin is an adipose tissue-derived secretory hormone whose plasma concentrations are lower in obese individuals. Obesity is a risk factor for the development and growth of pancreatic cancer, and hypoadiponectinemia was suggested to be involved in the growth of Pan02 murine pancreatic cancer cells that were inoculated into the flanks of congenitally obese mice.Aim
The aim of this study was to clarify the role of adiponectin in the growth of pancreatic cancer cells.Methods
We examined the effect of adiponectin on the growth of Pan02 cells using recombinant adiponectin and adiponectin knockout mice.Results
The in vitro treatment of Pan02 cells with adiponectin inhibited cellular proliferation that was accompanied by increased apoptosis and caspase-3 and caspase-7 activities. Transplantation of Pan02 cells into the pancreas of knockout mice resulted in a larger tumor volume with fewer terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells compared with wild-type mice.Conclusions
The results indicate that adiponectin directly suppresses the proliferation of Pan02 cells. 相似文献11.
Zhonghong Liu Yonghang Guo Juan Li Jun Xu Bingrong Liu 《Digestive diseases and sciences》2013,58(6):1590-1601
Introduction
Colorectal cancer is one of the common malignant tumors in humans, and the incidence rate is gradually increasing year by year. Survivin and CD44v3 are ideal targets for gene therapy due to their overexpression in colorectal cells. Studies show that downregulation of survivin could promote apoptosis and depress proliferation, and reduction of CD44v3 expression could inhibit tumor invasive capacity. It is difficult to achieve satisfactory curative effect.Objective
In this study, we use survivin and CD44v3 short hairpin RNAs (shRNA) combined transfection into colorectal cancer cell line SW480 to investigate its effects on the cell apoptosis, proliferation and invasiveness.Methods
ShRNA plasmids targeting survivin and CD44v3 were singly or co-transfected into SW480 cells.Results
The co-transfection group exhibited the most significant inhibitory effect on cell growth (P < 0.05) and the highest apoptosis rate (P < 0.05). In addition, the invasive capacity in the co-transfected group was the least. The tumor inhibition rate of the cotransfected group in xenograft tumor mice was significantly higher than other groups (P < 0.05). Moreover, the microvessel density of the co-transfected group was significantly decreased compared with other groups (P < 0.05).Conclusion
These results suggest combined transfection of survivin shRNA and CD44v3 shRNA may produce a synergistic effect on gene therapy in colorectal cancer. 相似文献12.
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Lei Yang Liang Yang Wencong Tian Jing Li Jie Liu Mengmeng Zhu Yan Zhang Yinan Yang Fei Liu Qiong Zhang Qianqian Liu Yanna Shen Zhi Qi 《Journal of cancer research and clinical oncology》2014,140(5):749-755
Purpose
Although the potential anticancer effect of resveratrol (RSV) on pancreatic cancer has been reported, its mechanism was not fully understood. The role of vascular endothelial growth factor B (VEGF-B) in cancer remains controversial. Herein, we aimed to examine whether the anticancer effect of RSV was related to the VEGF-B.Methods
The effect of RSV on pancreatic cancer cell line (capan-2 cells) was evaluated by CCK-8 assay, Hoechst 33342 staining, and flow cytometry. The mRNA level of VEGF-B was measured by real-time PCR. VEGF-B expression was knockdown by small interfering RNA (siRNA).The protein levels of VEGF-B, glycogen synthase kinase-3 beta (GSK-3β), and Bax were measured by Western blot.Results
Resveratrol treatment inhibited tumor growth, induced apoptosis, and up-regulated Bax expression in capan-2 cells. The mRNA and protein levels of VEGF-B were up-regulated after RSV treatment. However, VEGF-B siRNA treatment increased the apoptotic rate, and inhibited tumor activator GSK-3β, while Bax expression was not affected. The combination of RSV and VEGF-B siRNA showed significantly higher apoptotic rate in comparison with RSV or VEGF-B siRNA mono-treatment group.Conclusions
Resveratrol plays dual roles in pancreatic cancer: as a tumor suppressor via the up-regulation of Bax; as a tumor activator via the up-regulation of VEGF-B; and the anticancer effect of RSV is much stronger than the cancer promotion effect. The combination of RSV with pharmacological inhibitor of VEGF-B might, therefore, be a promising modality for clinical pancreatic cancer therapy. 相似文献14.
Fujikawa H Tanaka K Toiyama Y Saigusa S Inoue Y Uchida K Kusunoki M 《Journal of gastroenterology》2012,47(7):775-784
Background
The neurotrophic receptor tropomyosin related kinase (TrkB) is associated with tumor progression in neuroblastoma and certain human malignancies. Recent reports indicate TrkB may participate in the epithelial–mesenchymal transition (EMT). This study investigates whether TrkB expression is associated with the clinical outcome of colorectal cancer (CRC) patients and whether TrkB induces EMT in CRC cells.Methods
TrkB and E-cadherin expression in surgical tissue samples and clinicopathological data from 102 CRC patients were analyzed by real-time polymerase chain reaction and immunohistochemistry. The biological role of TrkB in CRC was analyzed using RNA interference against TrkB in the CRC cell line SW480 to assess tumor progression and the correlation between TrkB and E-cadherin expression.Results
Patients with high TrkB mRNA expression in clinical samples had a significantly poorer prognosis relative to those with low TrkB levels (p?=?0.03). TrkB was inversely correlated with E-cadherin at both the mRNA and protein levels. In vitro, cell proliferation (p?=?0.02), migration (p?0.001), and invasion (p?0.001) were significantly inhibited by TrkB knockdown while the anoikis rate increased in TrkB siRNA-transfected cells compared to control siRNA. Interestingly, E-cadherin expression in TrkB siRNA-transfected cells was higher than in control cells and vimentin was lower conversely.Conclusions
High TrkB expression is associated with poor prognosis in CRC patients and enhanced malignant potential in terms of proliferation, migration, invasion, and anoikis inhibition in CRC cells. These results indicate TrkB could induce EMT and play an important role in CRC progression to metastasis. 相似文献15.
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Yu Wang Yasushi Adachi Arisa Imsumran Hiroyuki Yamamoto Wenhua Piao Hua Li Masanori Ii Yoshiaki Arimura Mi Young Park Dalrae Kim Choon-Taek Lee David P. Carbone Kohzoh Imai Yasuhisa Shinomura 《Journal of gastroenterology》2010,45(2):159-170
Background and aims
Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling plays important parts in both the tumorigenicity and progression of digestive/gastrointestinal malignancies. In this study, we sought to test the effectiveness of a practical approach to blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses.Methods
We constructed a recombinant adenovirus expressing short hairpin RNA targeting IGF-IR (shIGF-IR) and assessed its effect on signal transduction, proliferation, and survival in digestive/gastrointestinal cancer cell lines representing colorectal, gastric, and pancreatic adenocarcinoma, esophageal squamous cell carcinoma, and hepatoma. We analyzed the effects of shIGF-IR alone and with chemotherapy in vitro and in nude mouse xenografts, as well as on insulin signaling and hybrid receptor formation between IGF-IR and insulin receptor.Results
shIGF-IR blocked expression and autophosphorylation of IGF-IR and downstream signaling by the IGFs, but not by insulin. shIGF-IR suppressed proliferation and carcinogenicity in vitro and up-regulated apoptosis in a dose-dependent fashion. shIGF-IR augmented the effects of chemotherapy on in vitro growth and apoptosis induction. Moreover, the combination of shIGF-IR and chemotherapy was highly effective against tumors in mice. shIGF-IR reduced hybrid receptor formation without effect on expression of insulin receptor.Conclusions
shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.18.
Xiaoqi Liu Siqi Li Faping Yi 《Journal of cancer research and clinical oncology》2014,140(8):1331-1341
Object
Trop2 plays an important role in proliferation and invasion of tumors. Extensive research has shown that the expression level of Trop2 is closely related to the progress of cervical diseases. This study was to explore the effects of Trop2 on cell proliferation and apoptosis in cervical cancer.Methods
Trop2 was knocked down by shRNA in CaSki cells. The expression level of mRNA and protein was detected by real-time PCR and western blot, respectively. Cell proliferation was determined by CCK-8 and clone formation assay; apoptosis was measured by flow cytometry; cell cycle and apoptosis-related proteins cyclinD1, P53, bcl-2, bax, caspase 3, 8 and 9 were analyzed as well to investigate possible mechanism.Results
Trop2 expression was effectively repressed in CaSki cells by Trop2 shRNA, which resulted in inhibition of proliferation and colony formation, whereas apoptosis rate was significantly increased. Furthermore, in Trop2 knockdown CaSki cells, the expression of cyclinD1 and bcl-2 was significantly down-regulated, while that of P53 and bax was up-regulated accompanied by increased activities of caspase 9 and 3 but not caspase 8.Conclusions
Trop2 is important in proliferation and apoptosis regulation in CaSki cells, which may become a novel target for cervical cancer treatment. 相似文献19.
Ning Liu Yuan-Yuan Sun Xiao-Wen Zhang Sheng Chen Ye Wang Zhao-Xiong Zhang Shao-Wei Song Guang-Bin Qiu Wei-Neng Fu 《Digestive diseases and sciences》2015,60(7):2000-2008
Background
miR-23a, which participates in invasion of pancreatic ductal adenocarcinoma cells into the mesothelial barrier, is a critical regulator in many cancers. It, however, is still unknown whether miR-23a regulates pancreatic cell proliferation and apoptosis or not.Aims
We sought to investigate the role of miR-23a in regulation of pancreatic cell proliferation and apoptosis.Methods
miRNA, mRNA, and protein expressions were determined by qRT-PCR and Western blot, respectively. Dual-luciferase reporter assay was used in detection for binding ability of miR-23a to APAF1. Ectopic miR-23a and APAF 1 were introduced to pancreatic cells, and their roles in proliferation and apoptosis were detected by MTT, colony formation, and apoptosis assays, respectively.Results
Up-regulation of miR-23a and down-regulation of APAF 1 were found in pancreatic ductal cancer, respectively. miR-23a significantly inhibited the luciferase activity by targeting APAF 1 3′UTR. Ectopic miR-23a significantly suppressed the APAF 1 gene expression in pancreatic cancer cells. Similar to siAPAF1, miR-23a significantly promoted pancreatic cancer cell proliferation and repressed apoptosis. Furthermore, miR-23a inhibitor and exogenous APAF 1 could recover the effects.Conclusions
It is suggested that miR-23a, acting as an oncogenic regulator by directly targeting APAF 1 in pancreatic cancer, is a useful potential biomarker in diagnosis and treatment of pancreatic cancer.20.
Jianghong Hu Yue Fang Yuan Cao Rong Qin Qiaoyun Chen 《Digestive diseases and sciences》2014,59(2):336-345