Title: Effects of cobalt chloride on mitochondrial damage and drug resistance of 5-FU-resistant human pancreatic cancer Patu8988/5-FU cell line
Abstract: Objective:To investigate the effects of mitochondrial damage and drug resistance of 5-FU-resistant human pancreatic cancer cell line Patu8988 / 5-FU cultured by cobalt chloride(CoCl2).Methods:Patu8988 / 5-FU were cultured in medium containing different concentrations of CoCl2(0,6.25 μmol / L,12.50 μmol / L,25.00 μmol / L,50.00 μmol / L,100.00 μmol / L,200.00 μmol / L,400.00 μmol / L).MTT assay was used to detect the cell proliferation activity and drug resistance of Patu8988 / 5-FU.JC-1 fluorescence staining with flow cytometry was used to analyze the mitochondria membrane potential.The mRNA expressions of HIF-1α and MDR1 were detected by RT-PCR technique.P-gp pump function of Patu8988 / 5-FU cells’ membrane was tested by Rh123.Results: With CoCl2 concentration rising or 100 μmol / L CoCl2 treatment time extension,the proliferation activity of Patu8988 / 5-FU cells was degressive,the depolarization of mitochondrial membrane potential was increased.Drug resistance index of Patu8988 / 5-FU to 5-FU in normoxia and hypoxia reaches to 28.11 ±3.19 and 52.08 ± 3.53,respectively(P 0.01).The mRNA expressions of HIF-1α and MDR1 in Patu8988 / 5-FU cells is higher in hypoxia than in normoxia(P 0.01).The accumulation amount of Rh123 in cytoplasm of Patu8988 / 5-FU cells was significantly lower in hypoxia than in normoxia(P 0.01).Conclusion:CoCl2 induced chemistry hypoxia of Patu8988 / 5-FU cells in a time-and-dose dependent manner.CoCl2 mimicing hypoxia dramatically increased resistance of Patu8988 / 5FU cells to 5-FU,and maybe through upregulating the expression of HIF-1α and MDR1.
Publication Year: 2012
Publication Date: 2012-01-01
Language: en
Type: article
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot