DOI QR코드

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)
  • 발행 : 2014.04.01

초록

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.

키워드

참고문헌

  1. 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
  2. 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
  3. 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
  4. 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.
  5. 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.
  6. 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
  7. 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
  8. 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.
  9. 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
  10. 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
  11. 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.
  12. Nelson K (2002). 3-Bromopyruvate kills cancer cells in animals. Lancet Oncol, 3, 524.
  13. 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
  14. 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
  15. 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
  16. 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
  17. Warburg O (1956). On the origin of cancer cells. Science, 123, 309-14. https://doi.org/10.1126/science.123.3191.309
  18. 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.
  19. 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
  20. 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
  21. 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.
  22. 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

피인용 문헌

  1. 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