肺癌細胞株に対するシスプラチンとカフェインの併用効果 [in Japanese] The Combination Effect of Caffeine and Cisplatin on a Human Lung Cancer Cell Line [in Japanese]
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ヒト肺腺癌細胞培養株PC9に対するCDDPとカフェインの併用効果を検討した.カフェイン2mM単独では細胞の増殖を強く抑制しなかったが、併用によりCDDP 1.0μg/mlの効果を増強した.FCMでのcell cycleの検討では、CDDPの負荷によりG_2+M期の蓄積を認め、カフェインの併用によりこのG_2+M期の貯蓄は減少した.FITCの蛍光量は48時間後に減少し、これはカフェイン単独, CDDPカフェイン併用ともに認められた.^3H-thymidineの取込みはCDDPの濃度の上昇とともに低下した.^<14>C-leucineの取り込みはカフェインの使用によって低下した.
It has been demonstrated that caffeine enhances the cytocidal effect of certain anticancer agents. The inhibition of DNA repair by caffeine has been considered to be one mechanism that enhances the cytocidal effect of such agents. The present study was conducted to clarify whether caffeine increases the effect of cisplatin (CDDP) on human lung adenocarcinoma cell line (PC9). CDDP concentrations used in this study were 1.0,2.0μg/ml. After one hour treatment with CDDP, cells were washed twice with PBS and incubated in RPMI1640/10%FBS (CAF(-)) or in RPMI1640/10%FBS supplemented with 2mM caffeine (CAF(+)). Cell viability was examined by means of cell growth curves and clonogenic assay. Cell cycle analysis was performed by the two color analysis with propidium iodide(PI) and fluorescein isothiocyanate (FITC) stain using a flow cytometer (FCM). The uptakes of ^3H-thymidine and ^<14>C-leucine were measured by means of the liquid scintillation method. The results are as follows. Caffeine enhanced the cytocidal effect of CDDP at 1.0μg/ml synergisticaly. Caffeine decreased the G_2M accumulation 24 hours after the CDDP exposure. Caffeine diminished fluorescence of FITC 48 hours after the CDDP exposure. The decrease of FITC fluorescence by caffeine was also observed in control. Caffeine decreased the uptake of ^<l4>C-leucine even in the control group which was not exposed to CDDP. From this data, we concluded that caffeine inhibits the protein synthesis in human lung cancer cells at a concentration which doesnot inhibit the growth of cancer cells significantly. Derangement of the protein synthesis might be the mode of caffeine-CDDP combination effect and it might give a hint as to the DNA repairing process.
- Japanese Journal of Lung Cancer
Japanese Journal of Lung Cancer 30(3), 341-349, 1990-06-20
The Japan Lung Cancer Society