Abstract 5242: Pancreatic cancer cell type specific oxygen dependent growth and drug sensitivity

Abstract

Abstract Most cell are cultured at 37°C, in 4% CO2 and 20% O2. Studies have shown that changing the temperature of the cell culture will lead to either cold shock or heat shock. Others have also shown that level of CO2 is crucial for pH balance in cell growth. Although cultured cells are exposed to 20% O2, oxygen tension in vivo is significantly lower in normal tissues ranging from 5 to 8% O2. Furthermore cancer tissues tend to be more hypoxic because of the poorly developed neo-vasculature. Hence, we sought to determine if pancreas cancer cells will grow and/or respond to drugs differently under 20% vs. 6% oxygen tension. Methods: Six pancreatic cancer cell lines were cultured in DMEM media with 10% FBS and 5% Penicillin in 4% CO2, 37°C with variable O2 conditions: 20% and 6%. Cells are plated onto 6-well plates. Triplicates of cells were trypsinized daily for 4 days for cell counts which was done by using hematocytometer. To test drug sensitivity, we used a known Lactate Dehydrogenase A (LDHA) inhibitor, FX11. LDHA inhibition has been shown to suppress tumor growth both in vitro and in vivo. Some cells were treated with an LDHA inhibitor, FX11 in varying concentrations: 5mM, 10mM and 20mM, while the controls were exposed to DMSO. Results: 1. Pancreas cancer cell lines E3, P215 and A6L grow better in 6% than in 20% oxygen level. 2. Pancreas cancer cell line A6L shows higher sensitivity to FX11 in 6% compared to 20% oxygen. 3. Pancreas cell line P215 shows lower sensitivity to FX11 in 6% compared to in 20% oxygen. Conclusion: The artificial nature of standard culture condition does not account for the significantly lower oxygen tension in vivo. Because cancer cell lines are established from tumors which tend to be hypoxic, measurements of cell growth rates and respond to therapeutic agents at 20% O2 may not reflect responses at 6% O2 and specifically not to in vivo conditions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5242. doi:1538-7445.AM2012-5242