- Volume 15 Issue 7
DOI QR Code
Inhibitory Effects of 3-Bromopyruvate on Human Gastric Cancer Implant Tumors in Nude Mice
- Xian, Shu-Lin (Department of Gastrointestine and Gland Surgery, the First Affiliated Hospital of Guangxi Medical University) ;
- Cao, Wei (Department of Gastrointestine and Gland Surgery, the First Affiliated Hospital of Guangxi Medical University) ;
- Zhang, Xiao-Dong (Department of Gastrointestine and Gland Surgery, the First Affiliated Hospital of Guangxi Medical University) ;
- Lu, Yun-Fei (Department of Gastrointestine and Gland Surgery, the First Affiliated Hospital of Guangxi Medical University)
- Published : 2014.04.01
Background: Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. Aim: To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Materials and Methods: Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). Results: 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p<0.05), with no significant difference between the high dose and 5-FU groups (p>0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p<0.05); there was no significant difference between 5-FU group and medium dose group (p>0.05), but there was between the 5-FU and high dose groups (p<0.05). Conclusions: This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice.
3-bromopyruvate;gastric cancer;nude mice;inhibitory effect
Supported by : National Natural Science Foundation of China
- Zhang X, Varin E, Briand M, et al (2009). Novel therapy for malignant pleural mesothelioma based on anti-energetic effec: an experimental study using 3-bromopyruvate on nude mice. Anticancer Res, 29, 1249-54.
- Zuo X, Djordjevic JT, Bijosono OJ, et al (2011). Miltefosine induces apoptosis-like cell death in yeast via Cox9p in cytochrome c oxidase. Mol Pharm, 80, 476-85. https://doi.org/10.1124/mol.111.072322
- Parks SK, Mazure NM, Counillon L, et al (2013). Hypoxia promotes tumor cell survival in acidic conditions by preserving ATP levels. J Cell Physiol, 228, 1854-62. https://doi.org/10.1002/jcp.24346
- Liu XH, Zheng XF, Wang YL, et al (2009). Inhibitive effect of 3-bromopyruvic acid on human breast cancer MCF-7 cells involves cell cycle arrest and apoptotic induction. Chin Med J, 122, 1681-5.
- Nelson K (2002). 3-Bromopyruvate kills cancer cells in animals. Lancet Oncol, 3, 524.
- Ota S, Geschwind JF, Buijs M, et al (2013). Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer. Target Oncol, 8, 145-51. https://doi.org/10.1007/s11523-013-0273-x
- Pereira AP, Bacha T, Kyaw N, et al (2009). Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate. Biochem J, 417, 717-26. https://doi.org/10.1042/BJ20080805
- Sener A, Giroix MH, Dufrane SP, et al (1985). Anomeric specificity of hexokinase and glucokinase activities in liver and insulin-producing cells. Biochem J, 230, 345-51. https://doi.org/10.1042/bj2300345
- Warburg O (1956). On the origin of cancer cells. Science, 123, 309-14. https://doi.org/10.1126/science.123.3191.309
- Xian SL, Cao W, Lu YF (2013). Research on the inhibitive effect on human gastric cancer cell line SGC-7901. GuangDong Med in chinese, 23, 92-4.
- Xu J, Wang J, Xu B, et al (2013). Colorectal cancer cells refractory to anti-VEGF treatment are vulnerable to glycolytic blockade due to persistent impairment of mitochondria. Mol Cancer Ther, 12, 717-24. https://doi.org/10.1158/1535-7163.MCT-12-1016-T
- Zare A, Mahmoodi M, Mohammad K, et al (2013). Survival analysis of patients with gastric cancer undergoing surgery at the iran cancer institute: a method based on multi-state models. Asian Pac J Cancer Prev, 14, 6369-73. https://doi.org/10.7314/APJCP.2013.14.11.6369
- Ganapathy KS, Geschwind JF, Kunjithapatham R, et al (2010). 3-Bromopyruvate induces endoplasmic reticulum stress, overcomes autophagy and causes apoptosis in human HCC cell lines. Anticancer Res, 30, 923-35.
- Chesney J, Mitchell R, Benigni F, et al (1999). An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect. Proc Natl Acad Sci, 96, 3047-52. https://doi.org/10.1073/pnas.96.6.3047
- Danial NN, Gramm CF, Scorrano L, et al (2003). BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature, 424, 952-6. https://doi.org/10.1038/nature01825
- Ferraro E, Pulicati A, Cencioni MT, et al (2008). Apoptosome-deficient cells lose cytochrome c through proteasomal degradation but survive by autophagy-dependent glycolysis. Mol Biol Cell, 8, 3576-88.
- Ganapathy KS, Vali M, Kunjithapatham R, et al (2010). 3-bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy. Curr Pharm Biotechnol, 11, 510-7. https://doi.org/10.2174/138920110791591427
- Garber K (2004). Energy boost: the Warburg effect returns in a new theory of cancer. J Natl Cancer Inst, 96, 1805-6. https://doi.org/10.1093/jnci/96.24.1805
- Geschwind JF, Ko YH, Torbenson MS, et al (2002). Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production. Cancer Res, 62, 3909-13.
- Jiang W, Huang Y, Wang JP, et al (2013). The synergistic anticancer effect of artesunate combined with allicin in osteosarcoma cell line in vitro and in vivo. Asian Pac J Cancer Prev, 14, 4615-9. https://doi.org/10.7314/APJCP.2013.14.8.4615
- Kim KW, Chow O, Parikh K, et al (2014). Peritoneal carcinomatosis in patients with gastric cancer, and the role for surgical resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. Am J Surg, 207, 78-83. https://doi.org/10.1016/j.amjsurg.2013.04.010
- Cao X, Jia G, Zhang T, et al (2008). Non-invasive MRI tumor imaging and synergistic anticancer effect of HSP90 inhibitor and glycolysis inhibitor in RIP1-Tag2 transgenic pancreatic tumor model. Cancer Chemoth Pharm, 62, 985-94. https://doi.org/10.1007/s00280-008-0688-8
- In Vitro Activity of 3-Bromopyruvate, an Anticancer Compound, Against Antibiotic-Susceptible and Antibiotic-Resistant Helicobacter pylori Strains vol.11, pp.2, 2019, https://doi.org/10.3390/cancers11020229