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首页> 外文期刊>Life sciences >Cell kinetics-dependent antitumor effect of irinotecan hydrochloride induced by the synchronizing effect of hydroxyurea: cell kinetics and dosing time.
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Cell kinetics-dependent antitumor effect of irinotecan hydrochloride induced by the synchronizing effect of hydroxyurea: cell kinetics and dosing time.

机译：羟基脲的同步作用诱导的盐酸依立替康盐酸盐的细胞动力学依赖性抗肿瘤作用：细胞动力学和给药时间。

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摘要

Influence of hydroxyurea (HU) on the antitumor effect of irinotecan hydrochloride (CPT-11) was investigated in ICR male mice transplanted with sarcoma 180 cells (S-180). A single dose of CPT-11 (100 mg/kg) was injected at various times after a single dose of HU (300 mg/kg). The relative tumor weight varied significantly depending on the timing of CPT-11 injection after HU injection (P < 0.01). The higher antitumor effect of CPT-11 was observed when DNA synthesis of S-180 cells increased (20 hr), and the lower effect was observed when the DNA synthesis decreased (0 hr). The loss of body weight also varied significantly depending on the timing of CPT-11 injection after HU injection (P < 0.01). The toxicity of CPT-11 was higher when the inhibitory effect of HU on DNA synthesis of bone marrow cells was stronger (15 hr), and the lower toxicity was observed when the inhibitory effect was not observed (0 hr). The plasma SN-38 concentration at 2 hr after CPT-11 injection was higher at 20 hr after HU injection than at 0 hr after HU injection. The difference in plasma esterase activity between 0 hr and 20 hr after HU injection was regarded as the mechanism underlying the dosing time-dependent difference of the SN-38 concentration. These experiments suggest that HU can produce a different phase of cell cycle between tumor cells and normal cells. This leads to increase the antitumor effect of CPT-11 without increasing the adverse effect of the drug. It is essential to consider the dosing time in the two-drug combination therapy.
机译：在移植了肉瘤180细胞（S-180）的ICR雄性小鼠中研究了羟基脲（HU）对盐酸伊立替康（CPT-11）的抗肿瘤作用的影响。在单剂量HU（300 mg / kg）之后的不同时间注射CPT-11（100 mg / kg）单剂量。相对肿瘤重量随HU注射后CPT-11注射时间的不同而有显着差异（P <0.01）。当S-180细胞的DNA合成增加（20小时）时，观察到CPT-11较高的抗肿瘤作用，而当DNA合成减少（0小时）时，观察到较低的作用。 HU注射后，根据CPT-11注射时间的不同，体重减轻也有显着差异（P <0.01）。当HU对骨髓细胞DNA合成的抑制作用较强时（15小时），CPT-11的毒性较高，而未观察到抑制作用（0小时）时，CPT-11的毒性较低。 CPT-11注射后2小时的血浆SN-38浓度在HU注射后20小时要比HU注射后0小时高。 HU注射后0小时和20小时之间血浆酯酶活性的差异被认为是SN-38浓度剂量依赖性时间差异的基础。这些实验表明，HU可以在肿瘤细胞和正常细胞之间产生不同阶段的细胞周期。这导致增加CPT-11的抗肿瘤作用而不增加药物的副作用。在两种药物联合治疗中必须考虑给药时间。

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