AI Article Synopsis
- The study aimed to investigate how a specific human liver cancer cell line (QGY/CDDP) developed resistance to the chemotherapy drug cisplatin (CDDP).
- Researchers established the resistant cell line through gradual exposure to increased CDDP concentrations and assessed its drug sensitivity, growth rate, and cellular characteristics using various laboratory techniques.
- Findings revealed that the QGY/CDDP cells had stable resistance to CDDP, with changes in cell growth phases and reduced platinum accumulation; their resistance mechanisms appeared linked to increased levels of glutathione S-transferase-pi (GST-pi) rather than P-glycoprotein (P-gp) expression.
Article Abstract
Objective: To study the biological characteristics and resistant mechanisms of the cisplatin-resistant human hepatocellular carcinoma (HCC) cell line.
Methods: The study took place in the Department of Pharmacology, Chongqing Medical University, Chongqing, China, between April 2005 and November 2007. A resistant HCC cell line (QGY/CDDP) was established by stepwise increasing cisplatin (CDDP) concentration and intermittent administration. Drug-chemo sensitivity was detected by 3-4,5-dimethylthiazol-2yl-2,5- diphenyltetrazolium bromide (MTT) assay. Cell doubling time was determined by cell counting, and cell cycle analysis was performed by flow cytometric (FCM) assay. Intracellular platinum accumulation was detected by atomic absorption spectrometry and the expression of P-glycoprotein (P-gp) and glutathione S-transferase-pi (GST-pi) were analyzed by FCM assay.
Results: QGY/CDDP cell line was established after 3 months with stable resistance to CDDP and exhibited cross-resistance to many other chemotherapeutic agents. Compared with parental cell line, cell doubling time of QGY/CDDP prolonged; and the cell proportion decreased in S and G2/M-phase and increased in G0/G1-phase. In QGY/CDDP cells, intracellular platinum accumulation decreased and GST-pi expression increased, but P-gp expression kept stable.
Conclusion: QGY/CDDP cell line shows the typical and stable resistant phenotype and characteristics of resistant cells. Its mechanisms of resistance to CDDP may be mediated by reduced accumulation of intracellular platinum and higher GST-pi expression, but it is not associated with P-gp expression.
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