Topoisomerase I inhibitor (camptothecin)-induced apoptosis in human gastric cancer cells and the role of wild-type p53 in the enhancement of its cytotoxicity

2000 ◽  
Vol 11 (9) ◽  
pp. 757-764 ◽  
Author(s):  
Zun-Wu Zhang ◽  
Stephen E Patchett ◽  
Michael JG Farthing
2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Li Zhang ◽  
Qi Qi ◽  
Jianqiang Yang ◽  
Dongsheng Sun ◽  
Chunfeng Li ◽  
...  

Hydrogen sulfide (H2S) can be synthesized in mammalian cells by cystathionineγ-lyase (CSE) and/or cystathionineβ-synthase (CBS). Both CSE and CBS are expressed in rat gastric tissues but their role in human gastric neoplasia has been unclear. The aims of the present study were to detect CSE and CBS proteins in human gastric cancer and determine the effect of exogenous NaHS on the proliferation of gastric cancer cells. We found that both CSE and CBS proteins were expressed in human gastric cancer cells and upregulated in human gastric carcinoma mucosa compared with those in noncancerous gastric samples. NaHS induced apoptosis of gastric cancer cells by regulating apoptosis related proteins. Also, NaHS inhibited cancer cell migration and invasion. An antigastric cancer role of H2S is thus indicated.


Gut ◽  
1999 ◽  
Vol 44 (3) ◽  
pp. 366-371 ◽  
Author(s):  
M Ohashi ◽  
F Kanai ◽  
H Ueno ◽  
T Tanaka ◽  
K Tateishi ◽  
...  

BACKGROUND/AIMSGastric cancer is one of the most prevalent forms of cancer in East Asia. Point mutation of the p53 gene has been reported in more than 60% of cases of gastric cancer and can lead to genetic instability and uncontrolled cell proliferation. The purpose of this investigation was to evaluate the potential of p53 gene therapy for gastric cancer.METHODSThe responses of human gastric cancer cell lines, MKN1, MKN7, MKN28, MKN45, and TMK-1, to recombinant adenoviruses encoding wild type p53 (AdCAp53) were analysed in vitro. The efficacy of the AdCAp53 treatment for MKN1 and MKN45 subcutaneous tumours in nude mice was assessed in vivo.RESULTSp53-specific growth inhibition was observed in vitro in two of four gastric cancer cell lines with mutated p53, but not in the wild type p53 cell line. The mechanism of the killing of gastric cancer cells by AdCAp53 was found, by flow cytometric analysis and detection of DNA fragmentation, to be apoptosis. In vivo studies showed that the growth of subcutaneous tumours of p53 mutant MKN1 cells was significantly inhibited by direct injection of AdCAp53, but no significant growth inhibition was detected in the growth of p53 wild type MKN45 tumours.CONCLUSIONSAdenovirus mediated reintroduction of wild type p53 is a potential clinical utility in gene therapy for gastric cancers.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 53-53
Author(s):  
Yongping Liu ◽  
Yang Ling ◽  
Qiu feng Qi ◽  
Yaodong Pan

53 Background: HER2 amplification occurs in about 20% of gastric cancers, and trastuzumab in combination with cisplatin based chemotherapy has been reported to improve oncological outcomes in gastric and gastro-oesophageal junction cancer with HER2 gene amplification. The aim of this study was to evaluate the potentially useful combined antitumor efficacy of trastuzumab and platinum agents in gastric cancer cells and to elucidate further the mechanisms possibly involved in the interaction between the trastuzumab and platinum agents. Methods: Gene expression was determined by using real-time quantitative PCR in gastric cancer cell lines. The chemosensitivity of gastric cancer cells to platinum agents and the apoptotic effect of drugs in vitro were evaluated using cellTiter 96 Aqueous One Solution Cell Proliferation Assay kit and double staining with both Annexin-V-FITC and PI, respectively. Results: Treatment with 1.0μg/ml trastuzumab for 48h could significantly increase sensitivity of oxaliplatin or cisplatin in HER2 amplified gastric cancer cells, and the IC50 of oxaliplatin and cisplatin were reduced to about 3.29 times and 6.91 times, respectively. Apoptosis analysis also indicated that trastuzumab significantly increased both oxaliplatin and cisplatin-induced apoptosis in NCI-N87 cells. Analysis of telomere-related genes revealed that trastuzumab singly and pretreatment with trastuzumab for 48h followed by oxaliplatin or cisplatin for another 48h could significantly downregulate the mRNA expression of TPP1, TRF1, TRF2, TRF2IP, POT1 and TIN2 genes. Conclusions: Our results describe the potential role of low dose trastuzumab to increase sensitivity of oxaliplatin and cisplatin in HER2 amplified gastric cancer cells, which may be partially through downregulating the expression levels of telomere-related genes.


PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149120 ◽  
Author(s):  
Yanfei Jia ◽  
Haiji Sun ◽  
Hongqiao Wu ◽  
Huilin Zhang ◽  
Xiuping Zhang ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ruyue Tian ◽  
Hailun Jiang ◽  
Linlin Shao ◽  
Yang Yu ◽  
Qingdong Guo ◽  
...  

Gastric cancer (GC) is one of the most common and fatal malignancies worldwide. MicroRNAs (miRNAs) play a critical role in tumor initiation, proliferation, and metastasis of gastric cancer. miR193b has been identified as a tumor suppressor in a variety of tumor types; however, its role in gastric cancer is yet to be determined. Here, we found a significant downregulation of miR193b expression in both human gastric cancer tissues (p<0.05) and human gastric cancer cell lines (p<0.01). Furthermore, the expression level of miR193b correlated with the tumor type, tumor size, and clinical stage (p<0.05). In vitro, miR193b overexpression inhibited cell survival and induced apoptosis in GC cell lines, indicating that miR193b plays a role in the development of gastric cancer. KRAS was verified as the target of miR193b, and KRAS overexpression attenuated miR193b-induced apoptosis (p<0.05). Moreover, we found that the Akt pathway negatively regulated miR193b, also affecting apoptosis. Further analyses indicated that PIK3CA mutation and KRAS amplification are two mutually exclusive pathways (p<0.01), and we hypothesize that both two pathways could result in the carcinogenic overactivation of KRAS. Thus, our results suggest that the Akt-miR193b-KRAS axis may act as a mechanism affecting apoptosis in gastric cancer cells.


2013 ◽  
Vol 17 (2) ◽  
pp. 383-389 ◽  
Author(s):  
Liuqin Yang ◽  
Chunhui Lan ◽  
Yu Fang ◽  
Yafei Zhang ◽  
Jun Wang ◽  
...  

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