p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Liu, Jia,Wu, Ning,Ma, Lei-Na,Zhong, Jia-Teng,Liu, Ge,Zheng, Lan-Hong,Lin, Xiu-Kun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has been well recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependent apoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employed cancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA anti-tumor activity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggered by OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompanied by cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but not SP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibited Bcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependent ASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo, p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, we elucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated by OA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlying the antitumor activity of nutritional components.

Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis

Liu, Jia,Ge, Yang-Yang,Zhu, Hong-Cheng,Yang, Xi,Cai, Jing,Zhang, Chi,Lu, Jing,Zhan, Liang-Liang,Qin, Qin,Yang, Yan,Yang, Yue-Hua,Zhang, Hao,Chen, Xiao-Chen,Liu, Zhe-Ming,Ma, Jian-Xin,Cheng, Hong-Yan,S Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.

Adjuvant Radiotherapy after Breast Conserving Treatment for Breast Cancer:A Dosimetric Comparison between Volumetric Modulated Arc Therapy and Intensity Modulated Radiotherapy

Liu, Zhe-Ming,Ge, Xiao-Lin,Chen, Jia-Yan,Wang, Pei-Pei,Zhang, Chi,Yang, Xi,Zhu, Hong-Cheng,Liu, Jia,Qin, Qin,Xu, Li-Ping,Lu, Jing,Zhan, Liang-Liang,Cheng, Hong-Yan,Sun, Xin-Chen Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Radiotherapy is an important treatment of choice for breast cancer patients after breast-conserving surgery, and we compare the feasibility of using dual arc volumetric modulated arc therapy (VMAT2), single arc volumetric modulated arc therapy (VMAT1) and Multi-beam Intensity Modulated Radiotherapy (M-IMRT) on patients after breast-conserving surgery. Materials and Methods: Thirty patients with breast cancer (half right-sided and half left-sided) treated by conservative lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned with three different radiotherapy techniques: 1) VMAT1; 2) VMAT2; 3) M-IMRT. The distributions for the planning target volume (PTV) and organs at risk (OARs) were compared. Dosimetries for all the techniques were compared. Results: All three techniques satisfied the dose constraint well. VMAT2 showed no obvious difference in the homogeneity index (HI) and conformity index (CI) of the PTV with respect to M-IMRT and VMAT1. VMAT2 clearly improved the treatment efficiency and can also decrease the mean dose and V5Gy of the contralateral lung. The mean dose and maximum dose of the spinal cord and contralateral breast were lower for VMAT2 than the other two techniques. The very low dose distribution (V1Gy) of the contralateral breast also showed great reduction in VMAT2 compared with the other two techniques. For the ipsilateral lung of right-sided breast cancer, the mean dose was decreased significantly in VMAT2 compared with VMAT1 and M-IMRT. The V20Gy and V30Gy of the ipsilateral lung of the left-sided breast cancer for VMAT2 showed obvious reduction compared with the other two techniques. The heart statistics of VMAT2 also decreased considerably compared to VMAT1 and M-IMRT. Conclusions: Compared to the other two techniques, the dual arc volumetric modulated arc therapy technique reduced radiation dose exposure to the organs at risk and maintained a reasonable target dose distribution.

Molecular Cloning and Bioinformatic Analysis of SPATA4 Gene

Liu, Shang-Feng,Ai, Chao,Ge, Zhong-Qi,Liu, Hai-Luo,Liu, Bo-Wen,He, Shan,Wang, Zhao Korean Society for Biochemistry and Molecular Biol 2005 Journal of biochemistry and molecular biology Vol.38 No.6

Full-length cDNA sequences of four novel SPATA4 genes in chimpanzee, cow, chicken and ascidian were identified by bioinformatic analysis using mouse or human SPATA4 cDNA fragment as electronic probe. All these genes have 6 exons and have similar protein molecular weight and do not localize in sex chromosome. The mouse SPATA4 sequence is identified as significantly changed in cryptorchidism, which shares no significant homology with any known protein in swissprot databases except for the homologous genes in various vertebrates. Our searching results showed that all SPATA4 proteins have a putative conserved domain DUF1042. The percentages of putative SPATA4 protein sequence identity ranging from 30% to 99%. The high similarity was also found in 1 kb promoter regions of human, mouse and rat SPATA4 gene. The similarities of the sequences upstream of SPATA4 promoter also have a high proportion. The results of searching SymAtlas (http://symatlas.gnf.org/SymAtlas/) showed that human SPATA4 has a high expression in testis, especially in testis interstitial, leydig cell, seminiferous tubule and germ cell. Mouse SPATA4 was observed exclusively in adult mouse testis and almost no signal was detected in other tissues. The pI values of the protein are negative, ranging from 9.44 to 10.15. The subcellular location of the protein is usually in the nucleus. And the signal peptide possibilities for SPATA4 are always zero. Using the SNPs data in NCBI, we found 33 SNPs in human SPATA4 gene genomic DNA region, with the distribution of 29 SNPs in the introns. CpG island searching gives the data about CpG island, which shows that the regions of the CpG island have a high similarity with each other, though the length of the CpG island is different from each other.This research is a fundamental work in the fields of the bioinformational analysis, and also put forward a new way for the bioinformatic analysis of other genes.

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

Liu, Ying,Liu, Chuan-Xia,Wu, Zhong-Ting,Ge, Lin,Zhou, Hong-Mei Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

The purpose of this study was to construct a protein-protein interaction (PPI) network related to oral squamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were mined within the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. The seed proteins were expanded using the nearest neighbor expansion method to construct a PPI network through the Online Predicated Human Interaction Database (OPHID). The network was verified to be statistically significant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked. 38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork was then constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4, CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearest neighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteins and guide medical researchers in further pertinent studies.

Research of the Mechanism of Low Frequency Oscillation Based on Dynamic Damping Effect

Liu, Wenying,Ge, Rundong,Zhu, Dandan,Wang, Weizhou,Zheng, Wei,Liu, Fuchao The Korean Institute of Electrical Engineers 2015 Journal of Electrical Engineering & Technology Vol.10 No.4

For now, there are some low frequency oscillations in the power system which feature low frequency oscillation with positive damping and cannot be explained by traditional low frequency oscillation mechanisms. Concerning this issue, the dynamic damping effect is put forward on the basis of the power-angle curve and the study of damping torque in this article. That is, in the process of oscillation, damping will dynamically change and will be less than that of the stable operating point especially when the angle of the stable operating point and the oscillation amplitude are large. In a situation with weak damping, the damping may turn negative when the oscillation amplitude increases to a certain extent, which may result in an amplitude-increasing oscillation. Finally, the simulation of the two-machine two-area system verifies the arguments in this paper which may provide new ideas for the analysis and control of some unclear low frequency phenomena.

Isolation and Characterization of a cDNA Encoding Two Novel Heat-shock Factor OsHSF6 and OsHSF12 in Oryza Sativa L.

Liu, Jin-Ge,Yao, Quan-Hong,Zhang, Zhen,Peng, Ri-He,Xiong, Ai-Sheng,Xu, Fang,Zhu, Hong Korean Society for Biochemistry and Molecular Biol 2005 Journal of biochemistry and molecular biology Vol.38 No.5

As a crucial transcription factor family, heat-shock factors were mainly analyzed and characterized in tomato and Arabidopsis. In this study, we isolated two putative heat shock factors OsHSF6 and OsHSF12 that interact specifically with heat-shock element (HSE) from Oryza sativa L by yeast one-hybrid method. The full-length cDNA of OsHSF6 and OsHSF12 have 1074bp and 920bp open reading frame (ORF), respectively. Analysis of the deduced amino acid sequences revealed that OsHSF6 was a class A heat shock factor (HSF) with all the conserved sequence elements characteristic of heat stress transcription factor, while OsHSF12 was a class B HSF with C-terminal domain (CTD) lacking of AHA motif. Bioinformatic analysis showed that the sequences and structures of two HSFs' DNA binding domain (DBD) had a high similarity with LpHSF24. The results of RT-PCR indicated OsHSF6 gene was expressed immediately after rice plants exposure to heat stress, and the transcription of OsHSF6 gene accumulated primarily in immature seeds, roots and leaves. However, we did not find the transcription of OsHSF12 gene in different organs and growth periods. Our results implied that OsHSF6 might be function as a HSF regulating early expression of stress genes in response to heat shock, and OsHSF12 might be act as a synergistic factor to regulate the expression of down-stream genes.

Silencing of Rac3 Inhibits Proliferation and Induces Apoptosis of Human Lung Cancer Cells

Liu, Tie-Qin,Wang, Ge-Bang,Li, Zheng-Jun,Tong, Xiang-Dong,Liu, Hong-Xu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Background: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer (LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3 expression in human LC cells and the consequences for cell survival. Materials and Methods: Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and protein expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by annexin V-APC /propidium iodide staining. Results: Efficient silencing of Rac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumor growth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess accumulation of cells in the G1 and S phase. Conclusions: Thus, functional analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.

Effects of Daidzein on mRNA Expression of Gonadotropin Receptors and P450 Aromatase in Ovarian Follicles of White Silky Fowls

Liu, Hongyun,Zhang, Caiqiao,Ge, Chutian,Liu, Jianxin Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.12

Effects of daidzein on expression of mRNAs of gonadotropin receptors (FSHR, LHR) and P450 aromatase (P450arom) were evaluated in ovarian follicles of white silky fowls. The hens were 13 months old in the post-peak period of egg laying and were randomly allocated as control and daidzein-treated groups, with daidzein supplemented to the basal diet at 10 mg/kg for 7 consecutive weeks. The mRNA expression of related genes was measured by semi-quantitative RT-PCR in the granulosa layers of the preovulatory follicle (PRF: F1, F2 ...) and follicular layers of the small yellow follicle (SYF), large white follicle (LWF) and atretic follicle (ATF). Results showed that daidzein supplementation significantly increased the number of SYF and LWF (p<0.05). The relative abundance of the FSHR mRNA decreased in the granulosa layers from F3 to F1, but LHR mRNA displayed opposite developmental changes. P450arom mRNA was highest in the SYF, but was very low in the granulosa layers after follicles finished selection. Treatment with daidzein resulted in increased mRNA expression of FSHR in F3 granulosa layer, LHR in granulosa layers of F3 to F1 and P450arom in LWF (p<0.05). These results indicated that dietary supplementation of daidzein up-regulated mRNA expression of gonadotropin receptors and P450arom to improve the development of preovulatory follicles in white silky fowls after the peak-laying period.

Effect of defect types in monolayer MoS2 on SO2 adsorption

Liu Ge,Liu Jianfei,Yan Jun,Chen Yunlin,Zhu Yabin,Tian Yahui 한국물리학회 2022 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.81 No.5

As a two-dimensional semiconductor material, molybdenum disulfde (MoS2) is extensively applied to sulfur dioxide (SO2) gas sensor. However, point defects will inevitably be produced in the preparation of MoS2, which signifcantly afect the adsorption properties of MoS2. Thus, understanding the properties of diferent point defects is essential for the successful application of MoS2. In this work, four types of point defects (VS-MoS2, VS2-MoS2, VMoS3-MoS2 and VMoS6-MoS2) of monolayers MoS2 were proposed, and the adsorption characteristics of SO2 on four typical defective MoS2 monolayers were investigated based on frst principles. The adsorption models were established to calculate the electronic properties and adsorption parameters of the adsorption systems. The results show that VMoS6-MoS2 defect has excellent adsorption properties for SO2 due to its largest adsorption energy, charge transfer and electrical response. The obtained results will contribute to the understanding of the efects on the MoS2 monolayers with diferent defects for SO2 sensing application.