Annals of Surgical Treatment and Research

The Korean Surgical Society (대한외과학회)
권호 표지

Effect of Antibiotics on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions

저산소 조건에서 항생제들이 인간 간암 세포의 생존에 미치는 영향

Lee, Young-Tag;Han, Mee-Jung;Lim, Sun-Ha;Park, Sung-Hwan;Suh, Hun Suk;Park, Jae-Bok;Kim, Yang-Il;Lee, Jongwon
이영탁;한미정;임선하;박성환;서헌석;박재복;김양일;이종원

  • Published : 20060000
⟨ Previous Next ⟩

Abstract

Purpose: Antibiotics that kill or suppress the growth of bacteria also affect tumors directly or indirectly. The authors aimed to show whether some antibiotics can improve cancer cell survival under hypoxic conditions, and how the antibiotics improve the cells under hypoxic conditions. Methods: Human hepatocellular carcinoma cells (HepG2) were grown at 1% oxygen concentration. Cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured at different incubation times, in the absence or presence of aminoglycosides, tetracyclines, quinolones, penicillins, cephalosporins, sulfonamides, or chloramphenicols. DNA fragmentation assay was performed to study the mechanism how some antibiotics improve the cell survival under hypoxic conditions. Results: Of the antibiotics tested, only aminoglycosides, tetracyclines, quinolones and the chloramphenicol improved cell survival under hypoxic conditions. Geneticin (G418), an aminoglycoside chosen as an example, improved cell survival even if glucose in the medium was completely consumed. At the same time, the appearance of DNA ladder was delayed in the presence of geneticin, which was also the same for the other antibiotics that improved cell survival under hypoxic conditions.Conclusion: Some antibiotics improved hepatocellular carcinoma cells under ischemic conditions by inhibiting apoptosis. The results implies that the antibiotics might adversely affect solid tumors, by improving cancer cell growth where hypoxic or ischemic conditions occur in the core region. Therefore, we might be cautious in choosing antibiotics for cancer patients with solid tumors, especially when the patients should be treated with antibiotics for a long time. (J Korean Surg Soc 2006;71:31-38)

Keywords

References

  1. Page C, Curtis M, Sutter M, Walker M, Hoffman B. Integrated Pharmacology. 2nd ed. Edinburgh: Mosby; 2002
  2. Velicer CM, Lampe JW, Heckbert SR, Potter JD, Taplin SH. Hypothesis: is antibiotic use associated with breast cancer- Cancer Causes Control 2003;14:739-47 https://doi.org/10.1023/A:1026323424792
  3. Velicer CM, Heckbert SR, Lampe JW, Potter JD, Robertson CA, Taplin SH. Antibiotic use in relation to the risk of breat cancer. JAMA 2004;291:827-35 https://doi.org/10.1001/jama.291.7.827
  4. Knekt P, Adlercreutz H, Rissanen H, Aromaa A, Teppo L, Heliovaara M. Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer- Br J Cancer 2000;82:1107-10 https://doi.org/10.1054/bjoc.1999.1047
  5. Kaye JA, Jick H. Antibiotics and the risk of breast cancer. Epidemiololgy 2005;16:688-90 https://doi.org/10.1097/01.ede.0000172131.84877.42
  6. Ianaro A, Ialenti A, Maffia P, Sautebin L, Rombola L, Carnuccio R, et al. Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther 2000;292:156-63
  7. Thong YH, Ferrante A. Inhibition of mitogen-induced human lymphocyte proliferative responses by tetracycline analogues. Clin Exp Immunol 1979;35:443-6
  8. Brown JM. Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Mol Med Today 2000;6:157-62 https://doi.org/10.1016/S1357-4310(00)01677-4
  9. Brown JM. The hypoxic cell: a target for selective cancer therapy-eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res 1999;59:5863-70
  10. Knocke TH, Weitmann HD, Feldmann HJ, Selzer E, Potter R. Intratumoral pO2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix. Radiother Oncol 1999;53:99-104 https://doi.org/10.1016/S0167-8140(99)00139-5
  11. Nordsmark M, Loncaster J, Chou SC, Havsteen H, Lindegaard JC, Davidson SE, et al. Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma. Int J Radiat Oncol Biol Phys 2001;49:581-6 https://doi.org/10.1016/S0360-3016(00)01493-0
  12. Tsang RW, Fyles AW, Milosevic M, Syed A, Pintilie M, Levin W, et al. Interrlationship of proliferation and hypoxia in carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2000;46:95-9 https://doi.org/10.1016/S0360-3016(99)00408-3
  13. Bussink J, Kaanders JH, van der Kogel AJ. Tumor hypoxia at the micro-regional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers. Radiother Oncol 2003;67:3-15 https://doi.org/10.1016/S0167-8140(03)00011-2
  14. Wouters BG, Koritzinsky M, Chiu RK, Theys J, Buijsen J, Lambin P. Modulation of cell death in the tumor microenvironment. Semin Radiat Oncol 2003;13:31-41 https://doi.org/10.1053/srao.2003.50004